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A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element

Abstract

Transcriptional regulation of the BRCA1 proximal promoter has been suggested to play a role in the decreased expression of BRCA1 observed in sporadic breast cancer. Computer analysis of the sequence of the proximal promoter reveals the presence of a potential CREB site. We have identified CREB/ATF-1 as the factor interacting with this site in nuclear extracts from MCF-7 and T-47D cells. This site is shown to be important for the constitutive expression of the promoter in these cells, as well as in Hep G2 cells. Despite the presence of this site, the BRCA1 promoter is not responsive to cAMP induction. It appears that CREB acts as a constitutive positive element for BRCA1 expression and that any mechanism inactivating CREB function would have a dramatic effect on BRCA1 expression.

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References

  • Armstrong SA, Barry DA, Leggett RW, Mueller CR . 1997 J. Biol. Chem. 272: 13489–13495

  • Atlas E, Stramwasser M, Whiskin K, Mueller CR . 2000 Oncogene 19: 1933–1940

  • Catteau A, Harris WH, Xu CF, Solomon E . 1999 Oncogene 18: 1957–1965

  • Chapman MS, Verma IM . 1996 Nature 382: 678–679

  • Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, Lee WH . 1996 Cancer Res. 56: 3168–3172

  • Cui JQ, Shao N, Chai Y, Wang H, Reddy ES, Rao VN . 1998 Oncol. Rep. 5: 591–595

  • De Cesare D, Fimia GM, Sassone-Corsi P . 1999 Trends Biochem. Sci. 24: 281–285

  • Dobrovic A, Simpfendorfer D . 1997 Cancer Res. 57: 3347–3350

  • Dong L, Wang W, Wang F, Stoner M, Reed JC, Harigai M, Samudio I, Kladde MP, Vyhlidal C, Safe S . 1999 J. Biol. Chem. 274: 32099–32107

  • Eggers A, Siemann G, Blume R, Knepel W . 1998 J. Biol. Chem. 273: 18499–18508

  • Futreal PA, Liu Q, Shattuck-Eidens D, Cochran C, Harshman K, Tavtigian S, Bennett LM, Haugen-Strano A, Swensen J, Miki Y, et al. 1994 Science 266: 120–122

  • Hai T, Curran T . 1991 Proc. Natl. Acad. Sci. USA 88: 3720–3724

  • Husain A, He G, Venkatraman ES, Spriggs DR . 1998 Cancer Research 58: 1120–1123

  • Kobayashi M, Kawakami K . 1997 Biochem. Biophys. Res. Commun. 241: 169–174

  • Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM . 1999 Proc. Natl. Acad. Sci. USA 96: 11364–11369

  • Magdinier F, Billard LM, Wittmann G, Frappart L, Benchaib M, Lenoir GM, Guerin JF, Dante R . 2000 FASEB J. 14: 1585–1594

  • Magdinier F, Ribieras S, Lenoir GM, Frappart L, Dante R . 1998 Oncogene 17: 3169–3176

  • Mancini DN, Rodenhiser DI, Ainsworth PJ, O'Malley FP, Singh SM, Xing W, Archer TK . 1998 Oncogene 16: 1161–1169

  • Merajver SD, Pham TM, Caduff RF, Chen M, Poy EL, Cooney KA, Weber BL, Collins FS, Johnston C, Frank TS . 1995 Nature Genet. 9: 439–443

  • Miki Y, et al. 1994 Science 266: 66–71

  • Montminy MR, Bilezikjian LM . 1987 Nature 328: 175–178

  • Neuhausen SL, Marshall CJ . 1994 Cancer Res. 54: 6069–6072

  • Rice JC, Massey-Brown KS, Futscher BW . 1998 Oncogene 17: 1807–1812

  • Rice JC, Futscher BW . 2000 Nucleic. Acids Res. 28: 3233–3239

  • Rice JC, Ozcelik H, Maxeiner P, Andrulis I, Futscher BW . 2000 Carcinogenesis 21: 1761–1765

  • Sawada J, Simizu N, Suzuki F, Sawa C, Goto M, Hasegawa M, Imai T, Watanabe H, Handa H . 1999 J. Biol. Chem. 274: 35475–35482

  • Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD . 1997a Proc. Natl. Acad. Sci. USA 94: 5605–5610

  • Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM . 1997b Cell 88: 265–275

  • Scully R, Ganesan S, Brown M, De Caprio JA, Cannistra SA, Feunteun J, Schnitt S, Livingston DM . 1996 Science 272: 123–126

  • Shao N, Chai YL, Shyam E, Reddy P, Rao VN . 1996 Oncogene 13: 1–7

  • Shen SX, Weaver Z, Xu X, Li C, Weinstein M, Chen L, Guan XY, Ried T, Deng CX . 1998 Oncogene 17: 3115–3124

  • Snouwaert JN, Gowen LC, Latour AM, Mohn AR, Xiao A, DiBiase L, Koller BH . 1999 Oncogene 18: 7900–7907

  • Suen TC, Goss PE . 1999 J. Biol. Chem. 274: 31297–31304

  • Thakur S, Croce CM . 1999 J. Biol. Chem. 274: 8837–8843

  • Thompson ME, Jensen RA, Obermiller PS, Page DL, Holt JT . 1995 Nature Genet. 9: 444–450

  • Xu CF, Brown MA, Chambers JA, Griffiths B, Nicolai H, Solomon E . 1995 Hum. Mol. Genet. 4: 2259–2264

  • Xu CF, Chambers JA, Solomon E . 1997 J. Biol. Chem. 272: 20994–20997

  • Zhang H, Somasundaram K, Peng Y, Tian H, Bi D, Weber BL, el-Deiry WS . 1998 Oncogene 16: 1713–1721

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Acknowledgements

We would like to thank Jim Gore for his excellent technical assistance. This work was supported by a grant from the Canadian Breast Cancer Research Initiative and grant BC000072 from the US Department of Defense Breast Cancer Research Program. Additional support came from Cancer Care Ontario and the Queen's University Faculty of Medicine.

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Correspondence to Christopher R Mueller.

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Atlas, E., Stramwasser, M. & Mueller, C. A CREB site in the BRCA1 proximal promoter acts as a constitutive transcriptional element. Oncogene 20, 7110–7114 (2001). https://doi.org/10.1038/sj.onc.1204890

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