Egr-1 regulates the transcription of the BRCA1 gene by etoposide
1
조회
0
다운로드
6
인용
0
참고문헌
키워드
초록
The breast cancer susceptibility gene BRCA1 encodes a nuclear protein, which functions as a tumor suppressor and is involved in gene transcription and DNA repair processes. Many families with inherited breast and ovarian cancers have mutations in the BRCA1 gene. However, only a few studies have reported on the mechanism underlying the regulation of BRCA1 expression in humans. In this study, we investigated the transcriptional regulation of BRCA1 in HeLa cells treated with etoposide. We found that three Egr-1-binding sequences (EBSs) were located at −1031, −1005, and −385 within the enhancer region of the BRCA1 gene. Forced expression of Egr-1 stimulated the BRCA1 promoter activity. EMSA data showed that Egr-1 bound directly to the EBS within the BRCA1gene. Knockdown of Egr-1 through the expression of a small hairpin RNA (shRNA) attenuated etoposide-induced BRCA1promoter activity. We conclude that Egr-1 targets the BRCA1gene in HeLa cells exposed to etoposide.
Abstract
The breast cancer susceptibility gene BRCA1 encodes a nuclear protein, which functions as a tumor suppressor and is involved in gene transcription and DNA repair processes. Many families with inherited breast and ovarian cancers have mutations in the BRCA1 gene. However, only a few studies have reported on the mechanism underlying the regulation of BRCA1 expression in humans. In this study, we investigated the transcriptional regulation of BRCA1 in HeLa cells treated with etoposide. We found that three Egr-1-binding sequences (EBSs) were located at −1031, −1005, and −385 within the enhancer region of the BRCA1 gene. Forced expression of Egr-1 stimulated the BRCA1 promoter activity. EMSA data showed that Egr-1 bound directly to the EBS within the BRCA1gene. Knockdown of Egr-1 through the expression of a small hairpin RNA (shRNA) attenuated etoposide-induced BRCA1promoter activity. We conclude that Egr-1 targets the BRCA1gene in HeLa cells exposed to etoposide.
참고문헌 (23)
- Miki, Y., "A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1", Science, 266, pp.66~71 (1994)
- Zhong, Q., "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response", Science, 285, pp.747~750 (1999)
- Scully, R., "BRCA1 is a component of the RNA polymerase II holoenzyme. Proc. Natl. Acad. Sci. U. S. A", Proc. Natl. Acad. Sci. U.S.A, 94, pp.5605~5610 (1997)
- Pao, G. M., "CBP", p300 interact with and function as transcriptional coactivators of BRCA1, 2000, pp.97, 1020~1025
- Anderson, S. F., "BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A", Nat. Genet, 19, pp.254~256 (1998)
- Irminger-Finger, I., "The functions of breast cancer susceptibility gene 1 (BRCA1) product and its associated proteins", Biol. Chem, 380, pp.117~128 (1999)
- Somasundaram, K., "Breast cancer gene 1 (BRCA1): role in cell cycle regulation and DNA repair--perhaps through transcription", J. Cell Biochem, 88, pp.1084~1091 (2003)
- Tavtigian, S. V., "The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.", Nat. Genet, 12, pp.333~337 (1996)
- Welcsh, P. L, "BRCA1 and BRCA2 and the genetics of breast and ovarian cancer", Hum. Mol. Genet, 10, pp.705~713 (2001)
- Kroupis, C., "Development and applications of a real-time quantitative RT-PCR method (QRT-PCR) for BRCA1 mRNA", Clin. Biochem, 38, pp.50~57 (2005)
- Fan, S., "Down-regulation of BRCA1 and BRCA2 in human ovarian cancer cells exposed to adriamycin and ultraviolet radiation", Int. J. Cancer, 77, pp.600~609 (1998)
- Zhan, Q., "Caspase-3 mediated cleavage of BRCA1 during UV-induced apoptosis", Oncogene, 21, pp.5335~5345 (2002)
- Ha, S. A., "Transdifferentiation-inducing HCCR-1 oncogene", BMC Cell Biol, 11, pp.49~ (2010)
- Thomas, J. E., "Induction of phosphorylation on BRCA1 during the cell cycle and after DNA damage", Cell Growth. Differ, 8, pp.801~809 (1997)
- Sukhatme, V. P., "A zinc finger-encoding gene coregulated with c-fos during growth and differentiation, and after cellular depolarization", Cell, 53, pp.37~43 (1988)
- Liu, C., "Suppression of growth and transformation and induction of apoptosis by EGR-1", Cancer Gene. Ther, 5, pp.3~28 (1998)
- Ji-Ha Kim, "Estrogen receptor β stimulates Egr-1 transcription via MEK1", Erk, BMB Reports, pp.2011, 44(7)[DOI]
- Virolle, T., "The Egr-1 transcription factor directly activates PTEN during irradiation- induced signalling", Nat. Cell. Biol, 3, pp.1124~1128 (2001)
- Krones-Herzig, A., "Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence, controls replicative senescence", Proc. Natl. Acad. Sci. U.S.A, 100, pp.3233~3238 (2003)
- Choi, B. H., "p21 Waf1", Cip1 expression by curcumin in U-87MG human glioma cells: role of early growth response- 1 expression, 2008, pp.68, 1369~1377
- Thyss, R., "NF-kappaB", Egr-1, EMBO J, pp.2005, 24[DOI]
- Yuequn Wang, "ZNF424, a novel human KRAB", C2H2 zinc finger protein, suppresses NFAT and p21 pathway, 2010, pp.43(3), 212~218[DOI]
- Choi, B. H., "Transcriptional activation of the human Klotho gene by epidermal growth factor in HEK293 cells; role of Egr-1", Gene, 450, pp.121~127