Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast carcinomas - PubMed

Affiliations

• PMID: 10962436

Comparative Study

Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast carcinomas

K Yoshikawa et al. Int J Cancer. 2000.

Abstract

Breast cancer is one of the most common malignancies among women. The molecular mechanisms involved in breast carcinogenesis, however, remain to be elucidated. Although somatic mutation of BRCA1 is rare, BRCA1 protein expression is reduced in about 30% of sporadic breast carcinomas (Yoshikawa et al., Clin. Cancer Res., 5:1249-1261, 1999), indicating its possible involvement even in sporadic breast carcinogenesis. Among the BRCA1-interactive proteins are hRAD51 (a human homologue of Escherichia coli rec A protein), BARD1 (BRCA1-associated RING domain 1) and p53, all of which are involved in DNA repair. We have analyzed the expression patterns of the hRAD51, BARD1 and p53 proteins in five breast cancer cell lines, including a BRCA1-deficient cell line, and in 179 breast cancer tissue samples from Japanese women, including 113 sporadic, 47 hereditary (i.e., BRCA1 status unknown), and 19 BRCA1-associated cases. Of the 179 breast carcinomas, fifty-four (30%) exhibited reduced hRAD51 expression, and sixty-two (35%) exhibited p53 overexpression. On the other hand, reduced expression level of BARD1, and of hMSH2 and hMLH1, which are components of DNA mismatch-repair pathway and are involved in colorectal carcinogenesis, was observed respectively in only 10 (6%), 8 (5%) and 3 (2%) cases. The overall frequency of sporadic breast carcinomas with abnormal expression of either BRCA1 or the BRCA1-interactive proteins was 67% (76/113). These results indicate that there may be an important role for the BRCA1-associated DNA-repair pathway, not only in BRCA1-associated breast carcinomas, but also in sporadic breast carcinomas.

Similar articles

• Reduction of BRCA1 protein expression in Japanese sporadic breast carcinomas and its frequent loss in BRCA1-associated cases.

  Yoshikawa K, Honda K, Inamoto T, Shinohara H, Yamauchi A, Suga K, Okuyama T, Shimada T, Kodama H, Noguchi S, Gazdar AF, Yamaoka Y, Takahashi R. Yoshikawa K, et al. Clin Cancer Res. 1999 Jun;5(6):1249-61. Clin Cancer Res. 1999. PMID: 10389907

• Microsatellite instability in hereditary and sporadic breast cancers.

  Adem C, Soderberg CL, Cunningham JM, Reynolds C, Sebo TJ, Thibodeau SN, Hartmann LC, Jenkins RB. Adem C, et al. Int J Cancer. 2003 Nov 20;107(4):580-2. doi: 10.1002/ijc.11442. Int J Cancer. 2003. PMID: 14520695

• Protein expression and methylation of DNA repair genes hMLH1, hMSH2, MGMT and BRCA1 and their correlation with clinicopathological parameters and prognosis in basal-like breast cancer.

  Alkam Y, Mitomi H, Nakai K, Himuro T, Saito T, Takahashi M, Arakawa A, Yao T, Saito M. Alkam Y, et al. Histopathology. 2013 Nov;63(5):713-25. doi: 10.1111/his.12220. Epub 2013 Sep 5. Histopathology. 2013. PMID: 24004112

• Cancer genetics in the new era of molecular biology.

  Lynch HT, Fusaro RM, Lynch JF. Lynch HT, et al. Ann N Y Acad Sci. 1997 Dec 29;833:1-28. doi: 10.1111/j.1749-6632.1997.tb48588.x. Ann N Y Acad Sci. 1997. PMID: 9616736 Review.

• Molecular genetics of hereditary ovarian cancer.

  Boyd J. Boyd J. Oncology (Williston Park). 1998 Mar;12(3):399-406; discussion 409-10, 413. Oncology (Williston Park). 1998. PMID: 9534190 Review.

Cited by

• BLM and RAD51 genes polymorphism and susceptibility to breast cancer.

  Sassi A, Popielarski M, Synowiec E, Morawiec Z, Wozniak K. Sassi A, et al. Pathol Oncol Res. 2013 Jul;19(3):451-9. doi: 10.1007/s12253-013-9602-8. Epub 2013 Feb 13. Pathol Oncol Res. 2013. PMID: 23404160 Free PMC article.

• BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays.

  Mahmoud AM, Macias V, Al-Alem U, Deaton RJ, Kadjaksy-Balla A, Gann PH, Rauscher GH. Mahmoud AM, et al. PLoS One. 2017 Sep 1;12(9):e0184385. doi: 10.1371/journal.pone.0184385. eCollection 2017. PLoS One. 2017. PMID: 28863181 Free PMC article.

• RAD51 interconnects between DNA replication, DNA repair and immunity.

  Bhattacharya S, Srinivasan K, Abdisalaam S, Su F, Raj P, Dozmorov I, Mishra R, Wakeland EK, Ghose S, Mukherjee S, Asaithamby A. Bhattacharya S, et al. Nucleic Acids Res. 2017 May 5;45(8):4590-4605. doi: 10.1093/nar/gkx126. Nucleic Acids Res. 2017. PMID: 28334891 Free PMC article.

• Contribution of Radiation Sensitive Protein 51 Genotypes to Pterygium Risk in a Taiwanese Population.

  Hsia NY, Hu PS, Chuang CL, Mong MC, Chen HC, Tsai CW, Wang YC, Chen JC, Bau DT, Chang WS. Hsia NY, et al. In Vivo. 2024 Sep-Oct;38(5):2197-2204. doi: 10.21873/invivo.13683. In Vivo. 2024. PMID: 39187312 Free PMC article.

• TODRA, a lncRNA at the RAD51 Locus, Is Oppositely Regulated to RAD51, and Enhances RAD51-Dependent DSB (Double Strand Break) Repair.

  Gazy I, Zeevi DA, Renbaum P, Zeligson S, Eini L, Bashari D, Smith Y, Lahad A, Goldberg M, Ginsberg D, Levy-Lahad E. Gazy I, et al. PLoS One. 2015 Jul 31;10(7):e0134120. doi: 10.1371/journal.pone.0134120. eCollection 2015. PLoS One. 2015. PMID: 26230935 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Research Materials

  • NCI CPTC Antibody Characterization Program
  • National BioResource Project

• Miscellaneous

  • NCI CPTAC Assay Portal