Skip to main content
Top
Published in: Virchows Archiv 4/2011

01-04-2011 | Original Article

Analysis of select members of the E26 (ETS) transcription factors family in colorectal cancer

Authors: Candida Deves, Daiana Renck, Bernardo Garicochea, Vinicius Duval da Silva, Tiago Giulianni Lopes, Henrique Fillman, Lucio Fillman, Silvana Lunardini, Luis Augusto Basso, Diogenes Santiago Santos, Eraldo L. Batista Jr.

Published in: Virchows Archiv | Issue 4/2011

Login to get access

Abstract

The E-twenty-six (ETS) family of transcription factors is known to act as positive or negative regulators of the expression of genes that are involved in diverse biological processes, including those that control cellular proliferation, differentiation, hematopoiesis, apoptosis, metastasis, tissue remodeling, and angiogenesis. Identification of target gene promoters of normal and oncogenic transcription factors provides new insights into the regulation of genes that are involved in the control of normal cell growth and differentiation. The aim of the present investigation was to analyze the differential expression of 11 ETS (ELF-3, ESE3, ETS1, ETV3, ETV4, ETV6, NERF, PDEF, PU1, Spi-B, and Spi-C) as potential markers for prognostic of colorectal cancer. A series of paired tissue biopsies consisting of a tumor and a non-affected control sample were harvested from 28 individuals suffering from diagnosed colorectal lesions. Total RNA was isolated from the samples, and after reverse transcription, differential expression of the select ETS was carried out through real-time polymerase chain reaction. Tumor staging as determined by histopathology was carried out to correlate the degree of tumor invasiveness with the expression of the ETS genes. The results demonstrated a different quantitative profile of expression in tumors and normal tissues. ETV4 was significantly upregulated with further increase in the event of lymph node involvement. PDEF and Spi-B presented downregulation, which was more significant when lymph node involvement was present. These findings were supported by immunohistochemistry of tumoral tissues. The results suggest that select ETS may serve as potential markers of colorectal cancer invasiveness and metastasis.
Literature
1.
go back to reference Sharrocks AD, Brown AL, Ling Y, Yates PR (1997) The ETS-domain transcription factor family. Int J Biochem Cell Biol 29(12):1371–1387PubMedCrossRef Sharrocks AD, Brown AL, Ling Y, Yates PR (1997) The ETS-domain transcription factor family. Int J Biochem Cell Biol 29(12):1371–1387PubMedCrossRef
2.
go back to reference Shindoh M, Higashino F, Kaya M, Yasuda M, Funaoka K, Hanzawa M, Hida K, Kohgo T, Amemiya A, Yoshida K, Fujinaga K (1996) Correlated expression of matrix metalloproteinases and ETS family transcription factor e1a-f in invasive oral squamous-cell-carcinoma-derived cell lines. Am J Pathol 148(3):693–700PubMed Shindoh M, Higashino F, Kaya M, Yasuda M, Funaoka K, Hanzawa M, Hida K, Kohgo T, Amemiya A, Yoshida K, Fujinaga K (1996) Correlated expression of matrix metalloproteinases and ETS family transcription factor e1a-f in invasive oral squamous-cell-carcinoma-derived cell lines. Am J Pathol 148(3):693–700PubMed
3.
go back to reference Graves BJ, Petersen JM (1998) Specificity within the ETS family of transcription factors. Adv Cancer Res 75:1–55PubMedCrossRef Graves BJ, Petersen JM (1998) Specificity within the ETS family of transcription factors. Adv Cancer Res 75:1–55PubMedCrossRef
4.
go back to reference Degnan BM, Degnan SM, Naganuma T, Morse DE (1993) The ETS multigene family is conserved throughout the metazoa. Nucleic Acids Res 21(15):3479–3484PubMedCrossRef Degnan BM, Degnan SM, Naganuma T, Morse DE (1993) The ETS multigene family is conserved throughout the metazoa. Nucleic Acids Res 21(15):3479–3484PubMedCrossRef
6.
go back to reference Hollenhorst PC, Jones DA, Graves BJ (2004) Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors. Nucleic Acids Res 32(18):5693–5702PubMedCrossRef Hollenhorst PC, Jones DA, Graves BJ (2004) Expression profiles frame the promoter specificity dilemma of the ETS family of transcription factors. Nucleic Acids Res 32(18):5693–5702PubMedCrossRef
7.
go back to reference Li R, Pei H, Watson DK (2000) Regulation of ETS function by protein–protein interactions. Oncogene 19(55):6514–6523PubMedCrossRef Li R, Pei H, Watson DK (2000) Regulation of ETS function by protein–protein interactions. Oncogene 19(55):6514–6523PubMedCrossRef
8.
go back to reference Sementchenko VI, Watson DK (2000) ETS target genes: past, present and future. Oncogene 19(55):6533–6548PubMedCrossRef Sementchenko VI, Watson DK (2000) ETS target genes: past, present and future. Oncogene 19(55):6533–6548PubMedCrossRef
9.
go back to reference Seth A, Watson DK (2005) ETS transcription factors and their emerging roles in human cancer. Eur J Cancer 41(16):2462–2478PubMedCrossRef Seth A, Watson DK (2005) ETS transcription factors and their emerging roles in human cancer. Eur J Cancer 41(16):2462–2478PubMedCrossRef
10.
go back to reference Hsu T, Trojanowska M, Watson DK (2004) ETS proteins in biological control and cancer. J Cell Biochem 91(5):896–903PubMedCrossRef Hsu T, Trojanowska M, Watson DK (2004) ETS proteins in biological control and cancer. J Cell Biochem 91(5):896–903PubMedCrossRef
11.
go back to reference Oikawa T, Yamada T (2003) Molecular biology of the ETS family of transcription factors. Gene 303:11–34PubMedCrossRef Oikawa T, Yamada T (2003) Molecular biology of the ETS family of transcription factors. Gene 303:11–34PubMedCrossRef
12.
go back to reference Sharrocks AD (2001) The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2(11):827–837PubMedCrossRef Sharrocks AD (2001) The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2(11):827–837PubMedCrossRef
13.
go back to reference Jedlicka P, Gutierrez-Hartmann A (2008) ETS transcription factors in intestinal morphogenesis, homeostasis and disease. Histol Histopathol 23(11):1417–1424PubMed Jedlicka P, Gutierrez-Hartmann A (2008) ETS transcription factors in intestinal morphogenesis, homeostasis and disease. Histol Histopathol 23(11):1417–1424PubMed
14.
go back to reference Turner DP, Findlay VJ, Moussa O, Watson DK (2007) Defining ETS transcription regulatory networks and their contribution to breast cancer progression. J Cell Biochem 102(3):549–559PubMedCrossRef Turner DP, Findlay VJ, Moussa O, Watson DK (2007) Defining ETS transcription regulatory networks and their contribution to breast cancer progression. J Cell Biochem 102(3):549–559PubMedCrossRef
15.
go back to reference Andersen CL, Jensen JL, Orntoft TF (2004) Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sETS. Cancer Res 64(15):5245–5250PubMedCrossRef Andersen CL, Jensen JL, Orntoft TF (2004) Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sETS. Cancer Res 64(15):5245–5250PubMedCrossRef
16.
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta c(t)) method. Methods 25(4):402–408PubMedCrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta c(t)) method. Methods 25(4):402–408PubMedCrossRef
17.
go back to reference Sobin LH, Wittekind C (2002) TNM classification of malignant tumors, 6th edn. Wiley, Washington Sobin LH, Wittekind C (2002) TNM classification of malignant tumors, 6th edn. Wiley, Washington
18.
go back to reference Boedefeld WM 2nd, Soong R, Weiss H, Diasio RB, Urist MM, Bland KI, Heslin MJ (2005) E1a-f is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7. Mol Carcinog 43(1):13–17PubMedCrossRef Boedefeld WM 2nd, Soong R, Weiss H, Diasio RB, Urist MM, Bland KI, Heslin MJ (2005) E1a-f is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7. Mol Carcinog 43(1):13–17PubMedCrossRef
19.
go back to reference Moss AC, Lawlor G, Murray D, Tighe D, Madden SF, Mulligan AM, Keane CO, Brady HR, Doran PP, MacMathuna P (2006) Etv4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion. Biochem Biophys Res Commun 345(1):216–221PubMedCrossRef Moss AC, Lawlor G, Murray D, Tighe D, Madden SF, Mulligan AM, Keane CO, Brady HR, Doran PP, MacMathuna P (2006) Etv4 and Myeov knockdown impairs colon cancer cell line proliferation and invasion. Biochem Biophys Res Commun 345(1):216–221PubMedCrossRef
20.
go back to reference Adachi Y, Yamamoto H, Itoh F, Arimura Y, Nishi M, Endo T, Imai K (2001) Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers. Int J Cancer 95(5):290–294PubMedCrossRef Adachi Y, Yamamoto H, Itoh F, Arimura Y, Nishi M, Endo T, Imai K (2001) Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers. Int J Cancer 95(5):290–294PubMedCrossRef
21.
go back to reference Horiuchi S, Yamamoto H, Min Y, Adachi Y, Itoh F, Imai K (2003) Association of ETS-related transcriptional factor e1af expression with tumour progression and overexpression of MMP-1 and matrilysin in human colorectal cancer. J Pathol 200(5):568–576PubMedCrossRef Horiuchi S, Yamamoto H, Min Y, Adachi Y, Itoh F, Imai K (2003) Association of ETS-related transcriptional factor e1af expression with tumour progression and overexpression of MMP-1 and matrilysin in human colorectal cancer. J Pathol 200(5):568–576PubMedCrossRef
22.
go back to reference Howe LR, Crawford HC, Subbaramaiah K, Hassell JA, Dannenberg AJ, Brown AM (2001) Pea3 is up-regulated in response to wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 276(23):20108–20115PubMedCrossRef Howe LR, Crawford HC, Subbaramaiah K, Hassell JA, Dannenberg AJ, Brown AM (2001) Pea3 is up-regulated in response to wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 276(23):20108–20115PubMedCrossRef
23.
go back to reference Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89(17):1260–1270PubMedCrossRef Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89(17):1260–1270PubMedCrossRef
24.
go back to reference Nosho K, Yoshida M, Yamamoto H, Taniguchi H, Adachi Y, Mikami M, Hinoda Y, Imai K (2005) Association of ETS-related transcriptional factor e1af expression with overexpression of matrix metalloproteinases, COX-2 and INOS in the early stage of colorectal carcinogenesis. Carcinogenesis 26(5):892–899PubMedCrossRef Nosho K, Yoshida M, Yamamoto H, Taniguchi H, Adachi Y, Mikami M, Hinoda Y, Imai K (2005) Association of ETS-related transcriptional factor e1af expression with overexpression of matrix metalloproteinases, COX-2 and INOS in the early stage of colorectal carcinogenesis. Carcinogenesis 26(5):892–899PubMedCrossRef
25.
go back to reference Chang CH, Scott GK, Kuo WL, Xiong X, Suzdaltseva Y, Park JW, Sayre P, Erny K, Collins C, Gray JW, Benz CC (1997) Esx: a structurally unique ETS overexpressed early during human breast tumorigenesis. Oncogene 14(13):1617–1622PubMedCrossRef Chang CH, Scott GK, Kuo WL, Xiong X, Suzdaltseva Y, Park JW, Sayre P, Erny K, Collins C, Gray JW, Benz CC (1997) Esx: a structurally unique ETS overexpressed early during human breast tumorigenesis. Oncogene 14(13):1617–1622PubMedCrossRef
26.
go back to reference Sapi E, Flick MB, Rodov S, Kacinski BM (1998) ETS-2 transdominant mutant abolishes anchorage-independent growth and macrophage colony-stimulating factor-stimulated invasion by bt20 breast carcinoma cells. Cancer Res 58(5):1027–1033PubMed Sapi E, Flick MB, Rodov S, Kacinski BM (1998) ETS-2 transdominant mutant abolishes anchorage-independent growth and macrophage colony-stimulating factor-stimulated invasion by bt20 breast carcinoma cells. Cancer Res 58(5):1027–1033PubMed
27.
go back to reference Maruta S, Sakai H, Kanda S, Hayashi T, Kanetake H, Miyata Y (2009) E1af expression is associated with extra-prostatic growth and matrix metalloproteinase-7 expression in prostate cancer. APMIS 117(11):791–796PubMedCrossRef Maruta S, Sakai H, Kanda S, Hayashi T, Kanetake H, Miyata Y (2009) E1af expression is associated with extra-prostatic growth and matrix metalloproteinase-7 expression in prostate cancer. APMIS 117(11):791–796PubMedCrossRef
28.
go back to reference Feldman RJ, Sementchenko VI, Gayed M, Fraig MM, Watson DK (2003) PDEF expression in human breast cancer is correlated with invasive potential and altered gene expression. Cancer Res 63(15):4626–4631PubMed Feldman RJ, Sementchenko VI, Gayed M, Fraig MM, Watson DK (2003) PDEF expression in human breast cancer is correlated with invasive potential and altered gene expression. Cancer Res 63(15):4626–4631PubMed
29.
go back to reference Nozawa M, Yomogida K, Kanno N, Nonomura N, Miki T, Okuyama A, Nishimune Y, Nozaki M (2000) Prostate-specific transcription factor hPSE is translated only in normal prostate epithelial cells. Cancer Res 60(5):1348–1352PubMed Nozawa M, Yomogida K, Kanno N, Nonomura N, Miki T, Okuyama A, Nishimune Y, Nozaki M (2000) Prostate-specific transcription factor hPSE is translated only in normal prostate epithelial cells. Cancer Res 60(5):1348–1352PubMed
30.
go back to reference Johnson TR, Koul S, Kumar B, Khandrika L, Venezia S, Maroni PD, Meacham RB, Koul HK (2010) Loss of PDEF, a prostate-derived ETS factor is associated with aggressive phenotype of prostate cancer: regulation of MMP 9 by PDEF. Mol Cancer 9:148PubMedCrossRef Johnson TR, Koul S, Kumar B, Khandrika L, Venezia S, Maroni PD, Meacham RB, Koul HK (2010) Loss of PDEF, a prostate-derived ETS factor is associated with aggressive phenotype of prostate cancer: regulation of MMP 9 by PDEF. Mol Cancer 9:148PubMedCrossRef
31.
go back to reference Anderson MK, Hernandez-Hoyos G, Diamond RA, Rothenberg EV (1999) Precise developmental regulation of ETS family transcription factors during specification and commitment to the T cell lineage. Development 126(14):3131–3148PubMed Anderson MK, Hernandez-Hoyos G, Diamond RA, Rothenberg EV (1999) Precise developmental regulation of ETS family transcription factors during specification and commitment to the T cell lineage. Development 126(14):3131–3148PubMed
32.
go back to reference Gallant S, Gilkeson G (2006) ETS transcription factors and regulation of immunity. Arch Immunol Ther Exp Warsz 54(3):149–163PubMedCrossRef Gallant S, Gilkeson G (2006) ETS transcription factors and regulation of immunity. Arch Immunol Ther Exp Warsz 54(3):149–163PubMedCrossRef
33.
go back to reference Bartholdy B, Du Roure C, Bordon A, Emslie D, Corcoran LM, Matthias P (2006) The ETS factor Spi-b is a direct critical target of the coactivator OBF-1. Proc Natl Acad Sci USA 103(31):11665–11670PubMedCrossRef Bartholdy B, Du Roure C, Bordon A, Emslie D, Corcoran LM, Matthias P (2006) The ETS factor Spi-b is a direct critical target of the coactivator OBF-1. Proc Natl Acad Sci USA 103(31):11665–11670PubMedCrossRef
34.
go back to reference Niini T, Vettenranta K, Hollmen J, Larramendy ML, Aalto Y, Wikman H, Nagy B, Seppanen JK, Ferrer Salvador A, Mannila H, Saarinen-Pihkala UM, Knuutila S (2002) Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia—a cDNA array study. Leukemia 16(11):2213–2221PubMedCrossRef Niini T, Vettenranta K, Hollmen J, Larramendy ML, Aalto Y, Wikman H, Nagy B, Seppanen JK, Ferrer Salvador A, Mannila H, Saarinen-Pihkala UM, Knuutila S (2002) Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia—a cDNA array study. Leukemia 16(11):2213–2221PubMedCrossRef
35.
go back to reference Talby L, Chambost H, Roubaud MC, N’Guyen C, Milili M, Loriod B, Fossat C, Picard C, Gabert J, Chiappetta P, Michel G, Schiff C (2006) The chemosensitivity to therapy of childhood early B acute lymphoblastic leukemia could be determined by the combined expression of CD34, Spi-b and BCR genes. Leuk Res 30(6):665–676PubMedCrossRef Talby L, Chambost H, Roubaud MC, N’Guyen C, Milili M, Loriod B, Fossat C, Picard C, Gabert J, Chiappetta P, Michel G, Schiff C (2006) The chemosensitivity to therapy of childhood early B acute lymphoblastic leukemia could be determined by the combined expression of CD34, Spi-b and BCR genes. Leuk Res 30(6):665–676PubMedCrossRef
36.
go back to reference Nagy M, Chapuis B, Matthes T (2002) Expression of transcription factors pu.1, Spi-b, Blimp-1, BSAP and oct-2 in normal human plasma cells and in multiple myeloma cells. Br J Haematol 116(2):429–435PubMedCrossRef Nagy M, Chapuis B, Matthes T (2002) Expression of transcription factors pu.1, Spi-b, Blimp-1, BSAP and oct-2 in normal human plasma cells and in multiple myeloma cells. Br J Haematol 116(2):429–435PubMedCrossRef
Metadata
Title
Analysis of select members of the E26 (ETS) transcription factors family in colorectal cancer
Authors
Candida Deves
Daiana Renck
Bernardo Garicochea
Vinicius Duval da Silva
Tiago Giulianni Lopes
Henrique Fillman
Lucio Fillman
Silvana Lunardini
Luis Augusto Basso
Diogenes Santiago Santos
Eraldo L. Batista Jr.
Publication date
01-04-2011
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 4/2011
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-011-1053-6

Other articles of this Issue 4/2011

Virchows Archiv 4/2011 Go to the issue