A Role for Candidate Tumor-suppressor Gene TCEAL7 in the Regulation of C-Myc Activity, Cyclin D1 Levels and Cellular Transformation

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2008 Sep 23

PMID 18806825

Citations 27

Authors

J Chien

K Narita

R Rattan

S Giri

R Shridhar

J Staub

D Beleford

J Lai

L R Roberts

J Molina

S H Kaufmann

G C Prendergast

V Shridhar

Affiliations

Soon will be listed here.

Abstract

The pathophysiological mechanisms that drive the development and progression of epithelial ovarian cancer remain obscure. Recently, we identified TCEAL7 as a transcriptional regulatory protein often downregulated in epithelial ovarian cancer. However, the biological significance of such downregulation in cancer is not currently known. Here, we show that TCEAL7 is downregulated frequently in many human cancers and that in immortalized human ovarian epithelial cells this event promotes anchorage-independent cell growth. Mechanistic investigations revealed that TCEAL7 associates with cyclin D1 promoter containing Myc E-box sequence and transcriptionally represses cyclin D1 expression. Moreover, downregulation of TCEAL7 promotes DNA-binding activity of Myc-Max, and upregulates the promoter activity of c-Myc-target gene, ornithine decarboxylase (ODC), whereas enhanced expression of TCEAL7 inhibits Myc-induced promoter activity of ODC. Our findings suggest that TCEAL7 may restrict ovarian epithelial cell transformation by limiting Myc activity. These results also suggest a potential, alternative mechanism by which c-Myc activity may be deregulated in cancer by the downregulation of TCEAL7.

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References

Nesbit C, Tersak J, Prochownik E . MYC oncogenes and human neoplastic disease. Oncogene. 1999; 18(19):3004-16. DOI: 10.1038/sj.onc.1202746. View

Elliott K, Sakamuro D, Basu A, Du W, Wunner W, Staller P . Bin1 functionally interacts with Myc and inhibits cell proliferation via multiple mechanisms. Oncogene. 1999; 18(24):3564-73. DOI: 10.1038/sj.onc.1202670. View

Bell D . Origins and molecular pathology of ovarian cancer. Mod Pathol. 2005; 18 Suppl 2:S19-32. DOI: 10.1038/modpathol.3800306. View

Nilsson J, Keller U, Baudino T, Yang C, Norton S, Old J . Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation. Cancer Cell. 2005; 7(5):433-44. DOI: 10.1016/j.ccr.2005.03.036. View

Westbrook T, Martin E, Schlabach M, Leng Y, Liang A, Feng B . A genetic screen for candidate tumor suppressors identifies REST. Cell. 2005; 121(6):837-48. DOI: 10.1016/j.cell.2005.03.033. View

Chien J, Staub J, Avula R, Zhang H, Liu W, Hartmann L . Epigenetic silencing of TCEAL7 (Bex4) in ovarian cancer. Oncogene. 2005; 24(32):5089-100. DOI: 10.1038/sj.onc.1208700. View

Massague J, Seoane J, Wotton D . Smad transcription factors. Genes Dev. 2005; 19(23):2783-810. DOI: 10.1101/gad.1350705. View

Budhram-Mahadeo V, Latchman D . Targeting Brn-3b in breast cancer therapy. Expert Opin Ther Targets. 2006; 10(1):15-25. DOI: 10.1517/14728222.10.1.15. View

Fukumoto M, Nakayama K . Ovarian epithelial tumors of low malignant potential: are they precursors of ovarian carcinoma?. Pathol Int. 2006; 56(5):233-9. DOI: 10.1111/j.1440-1827.2006.01960.x. View

10.

Chien J, Aletti G, Baldi A, Catalano V, Muretto P, Keeney G . Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity. J Clin Invest. 2006; 116(7):1994-2004. PMC: 1474818. DOI: 10.1172/JCI27698. View

11.

Gomis R, Alarcon C, Nadal C, Van Poznak C, Massague J . C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells. Cancer Cell. 2006; 10(3):203-14. DOI: 10.1016/j.ccr.2006.07.019. View

12.

Staub J, Chien J, Pan Y, Qian X, Narita K, Aletti G . Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance. Oncogene. 2007; 26(34):4969-78. DOI: 10.1038/sj.onc.1210300. View

13.

Grandori C, Cowley S, James L, Eisenman R . The Myc/Max/Mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol. 2000; 16:653-99. DOI: 10.1146/annurev.cellbio.16.1.653. View

14.

Baudino T, Cleveland J . The Max network gone mad. Mol Cell Biol. 2001; 21(3):691-702. PMC: 86661. DOI: 10.1128/MCB.21.3.691-702.2001. View

15.

Shridhar V, Lee J, Pandita A, ITURRIA S, Avula R, Staub J . Genetic analysis of early- versus late-stage ovarian tumors. Cancer Res. 2001; 61(15):5895-904. View

16.

Shridhar V, Sen A, Chien J, Staub J, Avula R, Kovats S . Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization. Cancer Res. 2002; 62(1):262-70. View

17.

Oster S, Ho C, Soucie E, Penn L . The myc oncogene: MarvelouslY Complex. Adv Cancer Res. 2002; 84:81-154. DOI: 10.1016/s0065-230x(02)84004-0. View

18.

Kalli K, Falowo O, Bale L, Zschunke M, Roche P, Conover C . Functional insulin receptors on human epithelial ovarian carcinoma cells: implications for IGF-II mitogenic signaling. Endocrinology. 2002; 143(9):3259-67. DOI: 10.1210/en.2001-211408. View

19.

Orian A, van Steensel B, Delrow J, Bussemaker H, Li L, Sawado T . Genomic binding by the Drosophila Myc, Max, Mad/Mnt transcription factor network. Genes Dev. 2003; 17(9):1101-14. PMC: 196053. DOI: 10.1101/gad.1066903. View

20.

Fernandez P, Frank S, Wang L, Schroeder M, Liu S, Greene J . Genomic targets of the human c-Myc protein. Genes Dev. 2003; 17(9):1115-29. PMC: 196049. DOI: 10.1101/gad.1067003. View