Skip to main content
Top
Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | Research article

Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

Authors: Bekim Sadikovic, Paul Thorner, Susan Chilton-MacNeill, Jeff W Martin, Nilva K Cervigne, Jeremy Squire, Maria Zielenska

Published in: BMC Cancer | Issue 1/2010

Login to get access

Abstract

Background

Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L.

Methods

Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts.

Results

RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders.

Conclusion

These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma.
Appendix
Available only for authorised users
Literature
1.
go back to reference Sakamoto A, Iwamoto Y: Current status and perspectives regarding the treatment of osteo-sarcoma: chemotherapy. Rev Recent Clin Trials. 2008, 3 (3): 228-231. 10.2174/157488708785700267.CrossRefPubMedPubMedCentral Sakamoto A, Iwamoto Y: Current status and perspectives regarding the treatment of osteo-sarcoma: chemotherapy. Rev Recent Clin Trials. 2008, 3 (3): 228-231. 10.2174/157488708785700267.CrossRefPubMedPubMedCentral
2.
go back to reference Gorlick R: Osteosarcoma: clinical practice and the expanding role of biology. Journal of musculoskeletal & neuronal interactions. 2002, 2 (6): 549-551. Gorlick R: Osteosarcoma: clinical practice and the expanding role of biology. Journal of musculoskeletal & neuronal interactions. 2002, 2 (6): 549-551.
3.
go back to reference Batanian JR, Cavalli LR, Aldosari NM, Ma E, Sotelo-Avila C, Ramos MB, Rone JD, Thorpe CM, Haddad BR: Evaluation of paediatric osteosarcomas by classic cytogenetic and CGH analyses. Mol Pathol. 2002, 55 (6): 389-393. 10.1136/mp.55.6.389.CrossRefPubMedPubMedCentral Batanian JR, Cavalli LR, Aldosari NM, Ma E, Sotelo-Avila C, Ramos MB, Rone JD, Thorpe CM, Haddad BR: Evaluation of paediatric osteosarcomas by classic cytogenetic and CGH analyses. Mol Pathol. 2002, 55 (6): 389-393. 10.1136/mp.55.6.389.CrossRefPubMedPubMedCentral
4.
go back to reference Lim G, Karaskova J, Beheshti B, Vukovic B, Bayani J, Selvarajah S, Watson SK, Lam WL, Zielenska M, Squire JA: An integrated mBAND and submegabase resolution tiling set (SMRT) CGH array analysis of focal amplification, microdeletions, and ladder structures consistent with breakage-fusion-bridge cycle events in osteosarcoma. Genes Chromosomes Cancer. 2005, 42 (4): 392-403. 10.1002/gcc.20157.CrossRefPubMed Lim G, Karaskova J, Beheshti B, Vukovic B, Bayani J, Selvarajah S, Watson SK, Lam WL, Zielenska M, Squire JA: An integrated mBAND and submegabase resolution tiling set (SMRT) CGH array analysis of focal amplification, microdeletions, and ladder structures consistent with breakage-fusion-bridge cycle events in osteosarcoma. Genes Chromosomes Cancer. 2005, 42 (4): 392-403. 10.1002/gcc.20157.CrossRefPubMed
5.
go back to reference Lim G, Karaskova J, Vukovic B, Bayani J, Beheshti B, Bernardini M, Squire JA, Zielenska M: Combined spectral karyotyping, multicolor banding, and microarray comparative genomic hybridization analysis provides a detailed characterization of complex structural chromosomal rearrangements associated with gene amplification in the osteosarcoma cell line MG-63. Cancer Genet Cytogenet. 2004, 153 (2): 158-164. 10.1016/j.cancergencyto.2004.01.016.CrossRefPubMed Lim G, Karaskova J, Vukovic B, Bayani J, Beheshti B, Bernardini M, Squire JA, Zielenska M: Combined spectral karyotyping, multicolor banding, and microarray comparative genomic hybridization analysis provides a detailed characterization of complex structural chromosomal rearrangements associated with gene amplification in the osteosarcoma cell line MG-63. Cancer Genet Cytogenet. 2004, 153 (2): 158-164. 10.1016/j.cancergencyto.2004.01.016.CrossRefPubMed
6.
go back to reference Sandberg AA, Bridge JA: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet. 2003, 145 (1): 1-30. 10.1016/S0165-4608(03)00105-5.CrossRefPubMed Sandberg AA, Bridge JA: Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: osteosarcoma and related tumors. Cancer Genet Cytogenet. 2003, 145 (1): 1-30. 10.1016/S0165-4608(03)00105-5.CrossRefPubMed
7.
go back to reference Selvarajah S, Yoshimoto M, Maire G, Paderova J, Bayani J, Squire JA, Zielenska M: Identification of cryptic microaberrations in osteosarcoma by high-definition oligonucleotide array comparative genomic hybridization. Cancer Genet Cytogenet. 2007, 179 (1): 52-61. 10.1016/j.cancergencyto.2007.08.003.CrossRefPubMed Selvarajah S, Yoshimoto M, Maire G, Paderova J, Bayani J, Squire JA, Zielenska M: Identification of cryptic microaberrations in osteosarcoma by high-definition oligonucleotide array comparative genomic hybridization. Cancer Genet Cytogenet. 2007, 179 (1): 52-61. 10.1016/j.cancergencyto.2007.08.003.CrossRefPubMed
8.
go back to reference Squire JA, Pei J, Marrano P, Beheshti B, Bayani J, Lim G, Moldovan L, Zielenska M: High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer. 2003, 38 (3): 215-225. 10.1002/gcc.10273.CrossRefPubMed Squire JA, Pei J, Marrano P, Beheshti B, Bayani J, Lim G, Moldovan L, Zielenska M: High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays. Genes Chromosomes Cancer. 2003, 38 (3): 215-225. 10.1002/gcc.10273.CrossRefPubMed
9.
go back to reference Zielenska M, Marrano P, Thorner P, Pei J, Beheshti B, Ho M, Bayani J, Liu Y, Sun BC, Squire JA, et al: High-resolution cDNA microarray CGH mapping of genomic imbalances in osteosarcoma using formalin-fixed paraffin-embedded tissue. Cytogenet Genome Res. 2004, 107 (1-2): 77-82. 10.1159/000079574.CrossRefPubMed Zielenska M, Marrano P, Thorner P, Pei J, Beheshti B, Ho M, Bayani J, Liu Y, Sun BC, Squire JA, et al: High-resolution cDNA microarray CGH mapping of genomic imbalances in osteosarcoma using formalin-fixed paraffin-embedded tissue. Cytogenet Genome Res. 2004, 107 (1-2): 77-82. 10.1159/000079574.CrossRefPubMed
10.
go back to reference Tang N, Song WX, Luo J, Haydon RC, He TC: Osteosarcoma development and stem cell differentiation. Clinical orthopaedics and related research. 2008, 466 (9): 2114-2130. 10.1007/s11999-008-0335-z.CrossRefPubMedPubMedCentral Tang N, Song WX, Luo J, Haydon RC, He TC: Osteosarcoma development and stem cell differentiation. Clinical orthopaedics and related research. 2008, 466 (9): 2114-2130. 10.1007/s11999-008-0335-z.CrossRefPubMedPubMedCentral
11.
go back to reference Thomas D, Kansara M: Epigenetic modifications in osteogenic differentiation and transformation. J Cell Biochem. 2006, 98 (4): 757-769. 10.1002/jcb.20850.CrossRefPubMed Thomas D, Kansara M: Epigenetic modifications in osteogenic differentiation and transformation. J Cell Biochem. 2006, 98 (4): 757-769. 10.1002/jcb.20850.CrossRefPubMed
12.
go back to reference Walkley CR, Qudsi R, Sankaran VG, Perry JA, Gostissa M, Roth SI, Rodda SJ, Snay E, Dunning P, Fahey FH, et al: Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 2008, 22 (12): 1662-1676. 10.1101/gad.1656808.CrossRefPubMedPubMedCentral Walkley CR, Qudsi R, Sankaran VG, Perry JA, Gostissa M, Roth SI, Rodda SJ, Snay E, Dunning P, Fahey FH, et al: Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 2008, 22 (12): 1662-1676. 10.1101/gad.1656808.CrossRefPubMedPubMedCentral
13.
go back to reference Gokgoz N, Wunder JS, Mousses S, Eskandarian S, Bell RS, Andrulis IL: Comparison of p53 mutations in patients with localized osteosarcoma and metastatic osteosarcoma. Cancer. 2001, 92 (8): 2181-2189. 10.1002/1097-0142(20011015)92:8<2181::AID-CNCR1561>3.0.CO;2-3.CrossRefPubMed Gokgoz N, Wunder JS, Mousses S, Eskandarian S, Bell RS, Andrulis IL: Comparison of p53 mutations in patients with localized osteosarcoma and metastatic osteosarcoma. Cancer. 2001, 92 (8): 2181-2189. 10.1002/1097-0142(20011015)92:8<2181::AID-CNCR1561>3.0.CO;2-3.CrossRefPubMed
14.
go back to reference Miller CW, Aslo A, Tsay C, Slamon D, Ishizaki K, Toguchida J, Yamamuro T, Lampkin B, Koeffler HP: Frequency and structure of p53 rearrangements in human osteosarcoma. Cancer research. 1990, 50 (24): 7950-7954.PubMed Miller CW, Aslo A, Tsay C, Slamon D, Ishizaki K, Toguchida J, Yamamuro T, Lampkin B, Koeffler HP: Frequency and structure of p53 rearrangements in human osteosarcoma. Cancer research. 1990, 50 (24): 7950-7954.PubMed
15.
go back to reference Radig K, Schneider-Stock R, Oda Y, Neumann W, Mittler U, Roessner A: Mutation spectrum of p53 gene in highly malignant human osteosarcomas. Gen Diagn Pathol. 1996, 142 (1): 25-32.PubMed Radig K, Schneider-Stock R, Oda Y, Neumann W, Mittler U, Roessner A: Mutation spectrum of p53 gene in highly malignant human osteosarcomas. Gen Diagn Pathol. 1996, 142 (1): 25-32.PubMed
16.
go back to reference Fuchs B, Pritchard DJ: Etiology of osteosarcoma. Clinical orthopaedics and related research. 2002, 397: 40-52. 10.1097/00003086-200204000-00007.CrossRefPubMed Fuchs B, Pritchard DJ: Etiology of osteosarcoma. Clinical orthopaedics and related research. 2002, 397: 40-52. 10.1097/00003086-200204000-00007.CrossRefPubMed
17.
go back to reference Deshpande A, Hinds PW: The retinoblastoma protein in osteoblast differentiation and osteosarcoma. Curr Mol Med. 2006, 6 (7): 809-817.PubMed Deshpande A, Hinds PW: The retinoblastoma protein in osteoblast differentiation and osteosarcoma. Curr Mol Med. 2006, 6 (7): 809-817.PubMed
18.
go back to reference Sadikovic B, Yoshimoto M, Al-Romaih K, Maire G, Zielenska M, Squire JA: In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma. PLoS ONE. 2008, 3 (7): e2834-10.1371/journal.pone.0002834.CrossRefPubMedPubMedCentral Sadikovic B, Yoshimoto M, Al-Romaih K, Maire G, Zielenska M, Squire JA: In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma. PLoS ONE. 2008, 3 (7): e2834-10.1371/journal.pone.0002834.CrossRefPubMedPubMedCentral
19.
go back to reference Sadikovic B, Yoshimoto M, Chilton-MacNeill S, Thorner P, Squire JA, Zielenska M: Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling. Hum Mol Genet. 2009, 18 (11): 1962-1975. 10.1093/hmg/ddp117.CrossRefPubMed Sadikovic B, Yoshimoto M, Chilton-MacNeill S, Thorner P, Squire JA, Zielenska M: Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling. Hum Mol Genet. 2009, 18 (11): 1962-1975. 10.1093/hmg/ddp117.CrossRefPubMed
20.
go back to reference Gamberi G, Benassi MS, Bohling T, Ragazzini P, Molendini L, Sollazzo MR, Pompetti F, Merli M, Magagnoli G, Balladelli A, et al: C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology. 1998, 55 (6): 556-563. 10.1159/000011912.CrossRefPubMed Gamberi G, Benassi MS, Bohling T, Ragazzini P, Molendini L, Sollazzo MR, Pompetti F, Merli M, Magagnoli G, Balladelli A, et al: C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology. 1998, 55 (6): 556-563. 10.1159/000011912.CrossRefPubMed
21.
go back to reference Wu JX, Carpenter PM, Gresens C, Keh R, Niman H, Morris JW, Mercola D: The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas. Oncogene. 1990, 5 (7): 989-1000.PubMed Wu JX, Carpenter PM, Gresens C, Keh R, Niman H, Morris JW, Mercola D: The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas. Oncogene. 1990, 5 (7): 989-1000.PubMed
22.
go back to reference Lu XY, Lu Y, Zhao YJ, Jaeweon K, Kang J, Xiao-Nan L, Ge G, Meyer R, Perlaky L, Hicks J, et al: Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. Mol Cancer Res. 2008, 6 (6): 937-946. 10.1158/1541-7786.MCR-07-2115.CrossRefPubMedPubMedCentral Lu XY, Lu Y, Zhao YJ, Jaeweon K, Kang J, Xiao-Nan L, Ge G, Meyer R, Perlaky L, Hicks J, et al: Cell cycle regulator gene CDC5L, a potential target for 6p12-p21 amplicon in osteosarcoma. Mol Cancer Res. 2008, 6 (6): 937-946. 10.1158/1541-7786.MCR-07-2115.CrossRefPubMedPubMedCentral
23.
go back to reference Maire G, Yoshimoto M, Chilton-MacNeill S, Thorner PS, Zielenska M, Squire JA: Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma. Neoplasia. 2009, 11 (3): 260-268. 263p following 268CrossRefPubMedPubMedCentral Maire G, Yoshimoto M, Chilton-MacNeill S, Thorner PS, Zielenska M, Squire JA: Recurrent RECQL4 imbalance and increased gene expression levels are associated with structural chromosomal instability in sporadic osteosarcoma. Neoplasia. 2009, 11 (3): 260-268. 263p following 268CrossRefPubMedPubMedCentral
24.
go back to reference Davicioni E, Wai DH, Anderson MJ: Diagnostic and prognostic sarcoma signatures. Molecular Diagnosis and Therapy. 2008, 12 (6): 359-374.CrossRefPubMed Davicioni E, Wai DH, Anderson MJ: Diagnostic and prognostic sarcoma signatures. Molecular Diagnosis and Therapy. 2008, 12 (6): 359-374.CrossRefPubMed
25.
go back to reference Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, Pintilie M, Jurisica I, Gilbert R, Gullane P, et al: Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Human Molecular Genetics. 2009 Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, Pintilie M, Jurisica I, Gilbert R, Gullane P, et al: Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma. Human Molecular Genetics. 2009
26.
go back to reference Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, et al: An integrated genomic analysis of human glioblastoma multiforme. Science. 2008, 321 (5897): 1807-1812. 10.1126/science.1164382.CrossRefPubMedPubMedCentral Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, et al: An integrated genomic analysis of human glioblastoma multiforme. Science. 2008, 321 (5897): 1807-1812. 10.1126/science.1164382.CrossRefPubMedPubMedCentral
27.
go back to reference McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis M, Olson JJ, Mikkelsen T, Lehman N, Aldape K, et al: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008 McLendon R, Friedman A, Bigner D, Van Meir EG, Brat DJ, Mastrogianakis M, Olson JJ, Mikkelsen T, Lehman N, Aldape K, et al: Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008
28.
go back to reference Rogers S, Cambrosio A: Making a new technology work: the standardization and regulation of microarrays. Yale Journal of Biology and Medicine. 2007, 80 (4): 165-178.PubMed Rogers S, Cambrosio A: Making a new technology work: the standardization and regulation of microarrays. Yale Journal of Biology and Medicine. 2007, 80 (4): 165-178.PubMed
29.
go back to reference Farragher SM, Tanney A, Kennedy RD, Paul Harkin D: RNA expression analysis from formalin fixed paraffin embedded tissues. Histochemistry and Cell Biology. 2008, 130 (3): 435-445. 10.1007/s00418-008-0479-7.CrossRefPubMed Farragher SM, Tanney A, Kennedy RD, Paul Harkin D: RNA expression analysis from formalin fixed paraffin embedded tissues. Histochemistry and Cell Biology. 2008, 130 (3): 435-445. 10.1007/s00418-008-0479-7.CrossRefPubMed
30.
go back to reference Li G, Zhang W, Zeng H, Chen L, Wang W, Liu J, Zhang Z, Cai Z: An integrative multi-platform analysis for discovering biomarkers of osteosarcoma. BMC Cancer. 2009, 9: 150-10.1186/1471-2407-9-150.CrossRefPubMedPubMedCentral Li G, Zhang W, Zeng H, Chen L, Wang W, Liu J, Zhang Z, Cai Z: An integrative multi-platform analysis for discovering biomarkers of osteosarcoma. BMC Cancer. 2009, 9: 150-10.1186/1471-2407-9-150.CrossRefPubMedPubMedCentral
31.
go back to reference Kresse SH, Ohnstad HO, Paulsen EB, Bjerkehagen B, Szuhai K, Serra M, Schaefer KL, Myklebost O, Meza-Zepeda LA: LSAMP, a novel candidate tumor suppressor gene in human osteosarcomas, identified by array comparative genomic hybridization. Genes, Chromosomes and Cancer. 2009, 48 (8): 679-693. 10.1002/gcc.20675.CrossRefPubMed Kresse SH, Ohnstad HO, Paulsen EB, Bjerkehagen B, Szuhai K, Serra M, Schaefer KL, Myklebost O, Meza-Zepeda LA: LSAMP, a novel candidate tumor suppressor gene in human osteosarcomas, identified by array comparative genomic hybridization. Genes, Chromosomes and Cancer. 2009, 48 (8): 679-693. 10.1002/gcc.20675.CrossRefPubMed
32.
go back to reference Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, Marcove RC, Lane JM, Mehta B, Urban C: Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982, 49 (6): 1221-1230. 10.1002/1097-0142(19820315)49:6<1221::AID-CNCR2820490625>3.0.CO;2-E.CrossRefPubMed Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, Marcove RC, Lane JM, Mehta B, Urban C: Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982, 49 (6): 1221-1230. 10.1002/1097-0142(19820315)49:6<1221::AID-CNCR2820490625>3.0.CO;2-E.CrossRefPubMed
33.
go back to reference Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M: Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol. 1994, 12 (12): 2699-2705.PubMed Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M: Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol. 1994, 12 (12): 2699-2705.PubMed
34.
go back to reference Fritsch MK, Bridge JA, Schuster AE, Perlman EJ, Argani P: Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue. Pediatr Dev Pathol. 2003, 6 (1): 43-53. 10.1007/s10024-002-0013-1.CrossRefPubMed Fritsch MK, Bridge JA, Schuster AE, Perlman EJ, Argani P: Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue. Pediatr Dev Pathol. 2003, 6 (1): 43-53. 10.1007/s10024-002-0013-1.CrossRefPubMed
35.
go back to reference Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25 (4): 402-408. 10.1006/meth.2001.1262.CrossRefPubMed Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25 (4): 402-408. 10.1006/meth.2001.1262.CrossRefPubMed
36.
go back to reference Bender R, Lange S: Adjusting for multiple testing--when and how?. Journal of clinical epidemiology. 2001, 54 (4): 343-349. 10.1016/S0895-4356(00)00314-0.CrossRefPubMed Bender R, Lange S: Adjusting for multiple testing--when and how?. Journal of clinical epidemiology. 2001, 54 (4): 343-349. 10.1016/S0895-4356(00)00314-0.CrossRefPubMed
37.
go back to reference Sadikovic B, Al-Romaih K, Squire JA, Zielenska M: Cause and consequences of genetic and epigenetic alterations in human cancer. Curr Genomics. 2008, 9 (6): 394-408. 10.2174/138920208785699580.CrossRefPubMedPubMedCentral Sadikovic B, Al-Romaih K, Squire JA, Zielenska M: Cause and consequences of genetic and epigenetic alterations in human cancer. Curr Genomics. 2008, 9 (6): 394-408. 10.2174/138920208785699580.CrossRefPubMedPubMedCentral
38.
go back to reference el-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, et al: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer research. 1994, 54 (5): 1169-1174.PubMed el-Deiry WS, Harper JW, O'Connor PM, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y, et al: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer research. 1994, 54 (5): 1169-1174.PubMed
39.
go back to reference Brazier H, Stephens S, Ory S, Fort P, Morrison N, Blangy A: Expression profile of RhoGTPases and RhoGEFs during RANKL-stimulated osteoclastogenesis: identification of essential genes in osteoclasts. J Bone Miner Res. 2006, 21 (9): 1387-1398. 10.1359/jbmr.060613.CrossRefPubMed Brazier H, Stephens S, Ory S, Fort P, Morrison N, Blangy A: Expression profile of RhoGTPases and RhoGEFs during RANKL-stimulated osteoclastogenesis: identification of essential genes in osteoclasts. J Bone Miner Res. 2006, 21 (9): 1387-1398. 10.1359/jbmr.060613.CrossRefPubMed
40.
go back to reference Carlo-Stella C, Lavazza C, Locatelli A, Vigano L, Gianni AM, Gianni L: Targeting TRAIL agonistic receptors for cancer therapy. Clin Cancer Res. 2007, 13 (8): 2313-2317. 10.1158/1078-0432.CCR-06-2774.CrossRefPubMed Carlo-Stella C, Lavazza C, Locatelli A, Vigano L, Gianni AM, Gianni L: Targeting TRAIL agonistic receptors for cancer therapy. Clin Cancer Res. 2007, 13 (8): 2313-2317. 10.1158/1078-0432.CCR-06-2774.CrossRefPubMed
41.
go back to reference Lian JB, Javed A, Zaidi SK, Lengner C, Montecino M, van Wijnen AJ, Stein JL, Stein GS: Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Critical Reviews in Eukaryotic Gene Expression. 2004, 14 (1-2): 1-41. 10.1615/CritRevEukaryotGeneExpr.v14.i12.10.CrossRefPubMed Lian JB, Javed A, Zaidi SK, Lengner C, Montecino M, van Wijnen AJ, Stein JL, Stein GS: Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Critical Reviews in Eukaryotic Gene Expression. 2004, 14 (1-2): 1-41. 10.1615/CritRevEukaryotGeneExpr.v14.i12.10.CrossRefPubMed
42.
go back to reference Zhang HY, Jin L, Stilling GA, Ruebel KH, Coonse K, Tanizaki Y, Raz A, Lloyd RV: RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors. Endocrine. 2009, 35 (1): 101-111. 10.1007/s12020-008-9129-z.CrossRefPubMed Zhang HY, Jin L, Stilling GA, Ruebel KH, Coonse K, Tanizaki Y, Raz A, Lloyd RV: RUNX1 and RUNX2 upregulate Galectin-3 expression in human pituitary tumors. Endocrine. 2009, 35 (1): 101-111. 10.1007/s12020-008-9129-z.CrossRefPubMed
43.
go back to reference Nakahara S, Oka N, Raz A: On the role of galectin-3 in cancer apoptosis. Apoptosis. 2005, 10 (2): 267-275. 10.1007/s10495-005-0801-y.CrossRefPubMed Nakahara S, Oka N, Raz A: On the role of galectin-3 in cancer apoptosis. Apoptosis. 2005, 10 (2): 267-275. 10.1007/s10495-005-0801-y.CrossRefPubMed
44.
go back to reference Khanna C, Khan J, Nguyen P, Prehn J, Caylor J, Yeung C, Trepel J, Meltzer P, Helman L: Metastasis-associated differences in gene expression in a murine model of osteosarcoma. Cancer research. 2001, 61 (9): 3750-3759.PubMed Khanna C, Khan J, Nguyen P, Prehn J, Caylor J, Yeung C, Trepel J, Meltzer P, Helman L: Metastasis-associated differences in gene expression in a murine model of osteosarcoma. Cancer research. 2001, 61 (9): 3750-3759.PubMed
45.
go back to reference Vladimirova V, Waha A, Luckerath K, Pesheva P, Probstmeier R: Runx2 is expressed in human glioma cells and mediates the expression of galectin-3. Journal of Neuroscience Research. 2008, 86 (11): 2450-2461. 10.1002/jnr.21686.CrossRefPubMed Vladimirova V, Waha A, Luckerath K, Pesheva P, Probstmeier R: Runx2 is expressed in human glioma cells and mediates the expression of galectin-3. Journal of Neuroscience Research. 2008, 86 (11): 2450-2461. 10.1002/jnr.21686.CrossRefPubMed
46.
go back to reference Blyth K, Vaillant F, Hanlon L, Mackay N, Bell M, Jenkins A, Neil JC, Cameron ER: Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer research. 2006, 66 (4): 2195-2201. 10.1158/0008-5472.CAN-05-3558.CrossRefPubMed Blyth K, Vaillant F, Hanlon L, Mackay N, Bell M, Jenkins A, Neil JC, Cameron ER: Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer research. 2006, 66 (4): 2195-2201. 10.1158/0008-5472.CAN-05-3558.CrossRefPubMed
47.
go back to reference Pregizer S, Baniwal SK, Yan X, Borok Z, Frenkel B: Progressive recruitment of Runx2 to genomic targets despite decreasing expression during osteoblast differentiation. Journal of Cellular Biochemistry. 2008, 105 (4): 965-970. 10.1002/jcb.21900.CrossRefPubMedPubMedCentral Pregizer S, Baniwal SK, Yan X, Borok Z, Frenkel B: Progressive recruitment of Runx2 to genomic targets despite decreasing expression during osteoblast differentiation. Journal of Cellular Biochemistry. 2008, 105 (4): 965-970. 10.1002/jcb.21900.CrossRefPubMedPubMedCentral
48.
go back to reference Maruyama Z, Yoshida CA, Furuichi T, Amizuka N, Ito M, Fukuyama R, Miyazaki T, Kitaura H, Nakamura K, Fujita T, et al: Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Developmental Dynamics. 2007, 236 (7): 1876-1890. 10.1002/dvdy.21187.CrossRefPubMed Maruyama Z, Yoshida CA, Furuichi T, Amizuka N, Ito M, Fukuyama R, Miyazaki T, Kitaura H, Nakamura K, Fujita T, et al: Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Developmental Dynamics. 2007, 236 (7): 1876-1890. 10.1002/dvdy.21187.CrossRefPubMed
49.
go back to reference Pratap J, Wixted JJ, Gaur T, Zaidi SK, Dobson J, Gokul KD, Hussain S, van Wijnen AJ, Stein JL, Stein GS, et al: Runx2 transcriptional activation of Indian Hedgehog and a downstream bone metastatic pathway in breast cancer cells. Cancer research. 2008, 68 (19): 7795-7802. 10.1158/0008-5472.CAN-08-1078.CrossRefPubMedPubMedCentral Pratap J, Wixted JJ, Gaur T, Zaidi SK, Dobson J, Gokul KD, Hussain S, van Wijnen AJ, Stein JL, Stein GS, et al: Runx2 transcriptional activation of Indian Hedgehog and a downstream bone metastatic pathway in breast cancer cells. Cancer research. 2008, 68 (19): 7795-7802. 10.1158/0008-5472.CAN-08-1078.CrossRefPubMedPubMedCentral
50.
go back to reference Dalla-Torre CA, Yoshimoto M, Lee CH, Joshua AM, de Toledo SR, Petrilli AS, Andrade JA, Chilton-MacNeill S, Zielenska M, Squire JA: Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer. 2006, 6: 237-10.1186/1471-2407-6-237.CrossRefPubMedPubMedCentral Dalla-Torre CA, Yoshimoto M, Lee CH, Joshua AM, de Toledo SR, Petrilli AS, Andrade JA, Chilton-MacNeill S, Zielenska M, Squire JA: Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer. 2006, 6: 237-10.1186/1471-2407-6-237.CrossRefPubMedPubMedCentral
51.
go back to reference Luo X, Chen J, Song WX, Tang N, Luo J, Deng ZL, Sharff KA, He G, Bi Y, He BC, et al: Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Lab Invest. 2008, 88 (12): 1264-1277. 10.1038/labinvest.2008.98.CrossRefPubMed Luo X, Chen J, Song WX, Tang N, Luo J, Deng ZL, Sharff KA, He G, Bi Y, He BC, et al: Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Lab Invest. 2008, 88 (12): 1264-1277. 10.1038/labinvest.2008.98.CrossRefPubMed
52.
go back to reference Lamour V, Detry C, Sanchez C, Henrotin Y, Castronovo V, Bellahcene A: Runx2- and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression. J Biol Chem. 2007, 282 (50): 36240-36249. 10.1074/jbc.M705833200.CrossRefPubMed Lamour V, Detry C, Sanchez C, Henrotin Y, Castronovo V, Bellahcene A: Runx2- and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression. J Biol Chem. 2007, 282 (50): 36240-36249. 10.1074/jbc.M705833200.CrossRefPubMed
53.
go back to reference Cleton-Jansen AM, Anninga JK, Briaire-de Bruijn IH, Romeo S, Oosting J, Egeler RM, Gelderblom H, Taminiau AH, Hogendoorn PC: Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumourigenic pathways. British journal of cancer. 2009, 101 (12): 2064-10.1038/sj.bjc.6605482.CrossRefPubMedPubMedCentral Cleton-Jansen AM, Anninga JK, Briaire-de Bruijn IH, Romeo S, Oosting J, Egeler RM, Gelderblom H, Taminiau AH, Hogendoorn PC: Profiling of high-grade central osteosarcoma and its putative progenitor cells identifies tumourigenic pathways. British journal of cancer. 2009, 101 (12): 2064-10.1038/sj.bjc.6605482.CrossRefPubMedPubMedCentral
54.
go back to reference Berger M, Muraro M, Fagioli F, Ferrari S: Osteosarcoma derived from donor stem cells carrying the Norrie's disease gene. N Engl J Med. 2008, 359 (23): 2502-2504. 10.1056/NEJMc0807172.CrossRefPubMed Berger M, Muraro M, Fagioli F, Ferrari S: Osteosarcoma derived from donor stem cells carrying the Norrie's disease gene. N Engl J Med. 2008, 359 (23): 2502-2504. 10.1056/NEJMc0807172.CrossRefPubMed
55.
go back to reference Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, et al: Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007, 25 (2): 371-379. 10.1634/stemcells.2005-0620.CrossRefPubMed Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, et al: Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007, 25 (2): 371-379. 10.1634/stemcells.2005-0620.CrossRefPubMed
Metadata
Title
Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy
Authors
Bekim Sadikovic
Paul Thorner
Susan Chilton-MacNeill
Jeff W Martin
Nilva K Cervigne
Jeremy Squire
Maria Zielenska
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-202

Other articles of this Issue 1/2010

BMC Cancer 1/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine