Abstract
Decreased expression of BRCA1 may play a role in the etiology of sporadic breast cancer. Deletion and point mutant analysis of proximal promoter elements in the BRCA1 1a promoter revealed a 22 bp region which was critical for the expression of the promoter in MCF-7 cells, but had a much reduced effect in T47D cells. The main transcription factor interacting with this site was identified as GABPα/β, and a discrete DNA binding complex was only observed in nuclear extracts from MCF-7 cells. Cotransfection experiments with GABPα and β1 expression vectors produced transactivation of this element in both lines. These results suggest that GABPα/β is a critical activator of BRCA1 expression, and that its activity may differ in human breast cell lines.
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References
Armstrong SA, Barry DA, Leggett RW and Mueller CR . 1997 J Biol Chem 272: 13489–13495
Baert JL, Monte D, Musgrove EA, Albagli O, Sutherland RL and de Launoit Y . 1997 Int J Cancer 70: 590–597
Boccia LM, Lillicrap DP, Newcombe K and Mueller CR . 1996 Mol Cell Biol 16: 1929–1935
Brown MA, Xu CF, Nicolai H, Griffiths B, Chambers JA, Black D and Solomon E . 1996 Oncogene 12: 2507–2513
Casey G . 1997 Curr Opin Oncol 9: 88–93
Catteau A, Harris WH, Xu CF and Solomon E . 1999 Oncogene 18: 1957–1965
de la Brousse FC, Birkenmeier EH, King DS, Rowe LB and McKnight SL . 1994 Genes Dev 8: 1853–1865
Dobrovic A and Simpfendorfer D . 1997 Cancer Res 57: 3347–3350
Favy DA, Rio P, Maurizis JC, Hizel C, Bignon YJ and Bernard-Gallon DJ . 1999 Biochem Biophys Res Commun 258: 284–291
Fromm L and Burden SJ . 1998 Genes Dev 12: 3074–3083
Futreal PA, Liu Q, Shattuck-Eidens D, Cochran C, Harshman K, Tavtigian S, Bennett LM, Haugen-Strano A, Swensen J, Miki Y, Eddington K, McClure M, Frye C, Weaver-Feldhaus J, Ding W, Gholami Z, Soderkvist P, Terry L, Jhanwar S, Berchuck A, Iglehart JD, Marks J, Ballinger DG, Barret JC, Skolnick MH, Kamp A and Wiseman R . 1994 Science 266: 120–122
Gudas JM, Li T, Nguyen H, Jensen D, Rauscher FJ and Cowan KH . 1996 Cell Growth Differ 7: 717–723
Hakem R, de la Pompa JL, Sirard C, Mo R, Woo M, Hakem A, Wakeham A, Potter J, Reitmair A, Billia F, Firpo E, Hui CC, Roberts J, Rossant J and Mak TW . 1996 Cell 85: 1009–1023
Hoare S, Copland JA, Wood TG, Jeng YJ, Izban MG and Soloff MS . 1999 Endocrinology 140: 2268–2279
Jarvis EM, Kirk JA and Clarke CL . 1998 Cancer Gene Cytogen 101: 109–115
Khurana TS, Rosmarin AG, Shang J, Krag TO, Das S and Gammeltoft S . 1999 Mol Biol Cell 10: 2075–2086
Lancaster JM, Wooster R, Mangion J, Phelan CM, Cochran C, Gumbs C, Seal S, Barfoot R, Collins N, Bignell G, Patel S, Hamoudi R, Larsson C, Wiseman RW, Berchuck A, Iglehart JD, Marks JR, Ashworth A, Stratton MR and Futreal PA . 1996 Nature Genet 13: 238–240
Lane TF, Deng C, Elson A, Lyu MS, Kozak CA and Leder P . 1995 Genes Dev 9: 2712–2722
Liu CY, Flesken-Nikitin A, Li S, Zeng Y and Lee WH . 1996 Genes Dev 10: 1835–1843
Magdinier F, Ribieras S, Lenoir GM, Frappart L and Dante R . 1998 Oncogene 17: 3169–3176
Mancini DN, Rodenhiser DI, Ainsworth PJ, O'Malley FP, Singh SM, Xing W and Archer TK . 1998 Oncogene 16: 1161–1169
Marks JR, Huper G, Vaughn JP, Davis PL, Norris J, McDonnell DP, Wiseman RW, Futreal PA and Iglehart JD . 1997 Oncogene 14: 115–121
Marquis ST, Rajan JV, Wynshaw-Boris A, Xu J, Yin GY, Abel KJ, Weber BL and Chodosh LA . 1995 Nature Gen 11: 17–26
Merajver SD, Pham TM, Caduff RF, Chen M, Poy EL, Cooney KA, Weber BL, Collins FS, Johnston C and Frank TS . 1995 Nature Genet 9: 439–443
Miki Y, Katagiri T, Kasumi F, Yoshimoto T and Nakamura Y . 1996 Nature Genet 13: 245–247
Nuchprayoon I, Simkevich CP, Luo M, Friedman AD and Rosmarin AG . 1997 Blood 89: 4546–4554
Ozcelik H, To MD, Couture J, Bull SB and Andrulis II . 1998 Int J Cancer 77: 1–6
Rice JC, Massey-Brown KS and Futscher BW . 1998 Oncogene 17: 1807–1812
Rio PG, Maurizis JC, Peffault dL, Bignon YJ and Bernard-Gallon DJ . 1999 Int J Cancer 80: 823–826
Sawa C, Goto M, Suzuki F, Watanabe H, Sawada J-I and Hanada H . 1996 Nucleic Acids Res 24: 4954–4961
Scott GK, Daniel JC, Xiong X, Maki RA, Kabat D and Benz CC . 1994 J Biol Chem 269: 19848–19858
Teng DH, Bogden R, Mitchell J, Baumgard M, Bell R, Berry S, Davis T, Ha PC, Kehrer R, Jammulapati S, Chen Q, Offit K, Skolnick MH, Tavtigian SV, Jhanwar S, Swedlund B, Wong AK and Kamb A . 1996 Nature Genet 13: 241–244
Thakur S and Croce CM . 1999 J Biol Chem 274: 8837–8843
Thompson ME, Jensen RA, Obermiller PS, Page DL and Holt JT . 1995 Nature Genet 9: 444–450
Tzahar E and Yarden Y . 1998 Biochim Biophys Acta 1377: M25–M37
Virbasius J, Virbasius C and Scarpulla R . 1993 Genes Dev 7: 380–392
Wilson CA, Ramos L, Villasenor MR, Anders KH, Press MF, Clarke K, Karlan B, Chen JJ, Scully R, Livingston D, Zuch RH, Kanter MH, Cohen S, Calzone FJ and Slamon DJ . 1999 Nature Genet 21: 236–240
Xu CF, Brown MA, Chambers JA, Griffiths B, Nicolai H and Solomon E . 1995 Human Mol Genet 4: 2259–2264
Xu CF, Brown MA, Nicolai H, Chambers JA, Griffiths BL and Solomon E . 1997a Human Mol Genet 6: 1057–1062
Xu CF, Chambers JA and Solomon E . 1997b J Biol Chem 272: 20994–20997
Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A and Deng CX . 1999 Nature Genet 22: 37–43
Yokomori N, Tawata M, Saito T, Shimura H and Onaya T . 1998 Mol Endocrinol 12: 1241–1249
Acknowledgements
This work was supported by a grant from the Canadian Breast Cancer Research Initiative. Additional support came from Cancer Care Ontario and the Queen's University Faculty of Medicine. We would like to thank Steve McKnight for the gift of the mouse GABP cDNAs and Drs J-I Sawada and H Hanada for the human GABP monoclonal antibodies.
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Atlas, E., Stramwasser, M., Whiskin, K. et al. GA-binding protein α/β is a critical regulator of the BRCA1 promoter. Oncogene 19, 1933–1940 (2000). https://doi.org/10.1038/sj.onc.1203516
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DOI: https://doi.org/10.1038/sj.onc.1203516
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