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International Orthopaedics

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01-10-2012 | Original Paper

Expression and significance of Kruppel-like factor 6 gene in osteosarcoma

Authors: Kai Chen, Yu Chen, Xiao-dong Zhu, Yu-shu Bai, Xian-zhao Wei, Chuan-feng Wang, Zi-qiang Chen, Ming Li

Published in: International Orthopaedics | Issue 10/2012

Abstract

Purpose

Osteosarcoma is primary malignant tumour of bone. Kruppel-like factor 6 (KLF6) is a tumor suppressor gene frequently inactivated in a number of human cancers and a ubiquitously expressed zinc-finger transcription factor. The present study aimed to first explore the relationship between the expression level of the KLF6 gene in osteosarcoma and the occurrence of bone tumours.

Methods

KLF6 mRNA and protein expression levels in osteosarcoma and normal bone tissue were assayed by real-time quantitative PCR and immunohistochemistry. KLF6 mRNA and protein expression levels in osteosarcoma cells and normal osteoblasts were detected by semi-quantitative reverse transcription PCR and Western blotting, respectively.

Results

Both the expression of KLF6 mRNA and protein in osteosarcoma cells and tissues were significantly lower than that in normal cells and tumour-adjacent tissues.

Conclusions

KLF6 is a putative tumor suppressor gene involved in osteosarcoma which can be used as a new therapeutic target and an important marker for early diagnosis and postoperative monitoring.

Longhi A, Errani C, Gonzales-Arabio D, Ferrari C, Mercuri M (2008) Osteosarcoma in patients older than 65 years. J Clin Oncol 26(33):5368–5373. doi:10.1200/JCO.2007.14.9104 PubMedCrossRef

Aljubran AH, Griffin A, Pintilie M, Blackstein M (2009) Osteosarcoma in adolescents and adults: survival analysis with and without lung metastases. Ann Oncol 20(6):1136–1141PubMedCrossRef

Bielack SS, Kempf-Bielack B, Delling G, Exner GU, Flege S, Helmke K, Kotz R, Salzer-Kuntschik M, Werner M, Winkelmann W, Zoubek A, Jürgens H, Winkler K (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols. JCO 20(3):15CrossRef

Tian Z, Quan X, Xu C, Dan L, Guo H, Leung W (2009) Hematoporphyrin monomethyl ether enhances the killing action of ultrasound on osteosarcoma in vivo. J Ultrasound Med 28(12):1695–1702PubMed

Serra M, Reverter-Branchat G, Maurici D, Benini S, Shen JN, Chano T, Hattinger CM, Manara MC, Pasello M, Scotlandi K, Picci P (2004) Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells. Ann Oncol 15(1):151–160PubMedCrossRef

Scionti I, Michelacci F, Pasello M, Hattinger CM, Alberghini M, Manara MC, Bacci G, Ferrari S, Scotlandi K, Picci P, Serra M (2008) Clinical impact of the methotrexate resistance-associated genes C-MYC and dihydrofolate reductase (DHFR) in high-grade osteosarcoma. Ann Oncol 19(8):1500–1508PubMedCrossRef

Bacci G, Briccoli A, Rocca M, Ferrari S, Donati D, Longhi A, Bertoni F, Bacchini P, Giacomini S, Forni C, Manfrini M, Galletti S (2003) Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Ann Oncol 14(7):1126–1134PubMedCrossRef

Fenech M (2005) The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and nutritional treatment of genome and epigenome damage on an individual basis. Mutagenesis 20(4):255–269PubMedCrossRef

Udler M, Maia AT, Cebrian A, Brown C, Greenberg D, Shah M, Caldas C, Dunning A, Easton D, Ponder B, Pharoah P (2007) Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer. J Clin Oncol 25(21):3015–3023PubMedCrossRef

10.

Komori T, Takemasa I, Yamasaki M, Motoori M, Kato T, Kikkawa N, Kawaguchi N, Ikeda M, Yamamoto H, Sekimoto M, Matsubara K, Matsuura N, Monden M (2008) Gene expression of colorectal cancer: preoperative genetic diagnosis using endoscopic biopsies. Int J Oncol 32(2):367–375PubMed

11.

Marina N, Gebhardt M, Teot L, Gorlick R (2004) Biology and therapeutic advances for pediatric osteosarcoma. Oncologist 9(4):422–441PubMedCrossRef

12.

Chiambaretta F, Nakamura H, De Graeve F, Sakai H, Marceau G, Maruyama Y, Rigal D, Dastugue B, Sugar J, Yue BY, Sapin V (2006) Kruppel-like factor 6 (KLF6) affects the promoter activity of the alpha1-proteinase inhibitor gene. Invest Ophthalmol Vis Sci 47(2):582–590PubMedCrossRef

13.

Bieker JJ (2001) Kruppel-like factors: three fingers in many pies. J Biol Chem 276(37):34355–34358PubMedCrossRef

14.

Rubinstein M, Idelman G, Plymate SR, Narla G, Friedman SL, Werner H (2004) Transcriptional activation of the insulin-like growth factor I receptor gene by the Kruppel-like factor 6 (KLF6) tumor suppressor protein: potential interactions between KLF6 and p53. Endocrinology 145(8):3769–3777PubMedCrossRef

15.

Reeves HL, Narla G, Ogunbiyi O, Haq AI, Katz A, Benzeno S, Hod E, Harpaz N, Goldberg S, Tal-Kremer S, Eng FJ, Arthur MJ, Martignetti JA, Friedman SL (2004) Kruppel-like factor 6 (KLF6) is a tumor-suppressor gene frequently inactivated in colorectal cancer. Gastroenterology 126(4):1090–1103PubMedCrossRef

16.

Camacho-Vanegas O, Narla G, Teixeira MS, DiFeo A, Misra A, Singh G, Chan AM, Friedman SL, Feuerstein BG, Martignetti JA (2007) Functional inactivation of the KLF6 tumor suppressor gene by loss of heterozygosity and increased alternative splicing in glioblastoma. Int Cancer 121(6):1390–1395CrossRef

17.

DiFeo A, Narla G, Hirshfeld J, Camacho-Vanegas O, Narla J, Rose SL, Kalir T, Yao S, Levine A, Birrer MJ, Bonome T, Friedman SL, Buller RE, Martignetti JA (2006) Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination. Clin Cancer Res 12(12):3730–3739PubMedCrossRef

18.

Sangodkar J, DiFeo A, Feld L, Bromberg R, Schwartz R, Huang F, Terzo EA, Choudhri A, Narla G (2009) Targeted reduction of KLF6-SV1 restores chemotherapy sensitivity in resistant lung adenocarcinoma. Lung Cancer 66(3):292–297PubMedCrossRef

19.

Narla G, Heath KE, Reeves HL, Li D, Giono LE, Kimmelman AC, Glucksman MJ, Narla J, Eng FJ, Chan AM, Ferrari AC, Martignetti JA, Friedman SL (2001) KLF6, a candidate tumor suppressor gene mutated in prostate cancer. Science 294(5551):2563–2566PubMedCrossRef

20.

Yamashita K, Upadhyay S, Osada M, Hoque MO, Xiao Y, Mori M, Sato F, Meltzer SJ, Sidransky D (2002) Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. Cancer Cell 2(6):485–495PubMedCrossRef

21.

Kremer-Tal S, Reeves HL, Narla G, Thung SN, Schwartz M, Difeo A, Katz A, Bruix J, Bioulac-Sage P, Martignetti JA, Friedman SL (2004) Frequent inactivation of the tumor suppressor Kruppel-like factor 6 (KLF6) in hepatocellular carcinoma. Hepatology 40(5):1047–1052PubMedCrossRef

22.

Fromowitz FB, Voilg MV, Chaos et al (1987) Ras P2l expression in the progression of brain cancer. Human Pathol 18(4):8

23.

Wikman H, Kettunen E, Seppanen JK, Karjalainen A, Hollmen J, Anttila S, Knuutila S (2002) Identification of differentially expressed genes in pulmonary adenocarcinoma by using cDNA array. Oncogene 21(37):5804–5813PubMedCrossRef

24.

Yin D, Komatsu N, Miller CW, Chumakov AM, Marschesky A, McKenna R, Black KL, Koeffler HP (2007) KLF6: mutational analysis and effect on cancer cell proliferation. Int J Oncol 30(1):65–72PubMed

25.

Benzeno S, Narla G, Allina J, Cheng GZ, Reeves HL, Banck MS, Odin JA, Diehl JA, Germain D, Friedman SL (2004) Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1. Cancer Res 64(11):3885–3891PubMedCrossRef

Title: Expression and significance of Kruppel-like factor 6 gene in osteosarcoma
Authors: Kai Chen
Yu Chen
Xiao-dong Zhu
Yu-shu Bai
Xian-zhao Wei
Chuan-feng Wang
Zi-qiang Chen
Ming Li
Publication date: 01-10-2012
Publisher: Springer-Verlag
Published in: International Orthopaedics / Issue 10/2012
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI: https://doi.org/10.1007/s00264-012-1626-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression and significance of Kruppel-like factor 6 gene in osteosarcoma

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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