Correlation between BRCA1 expression and apoptosis-related biological parameters in sporadic breast carcinomas.
BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian cancer syndrome. Increased evidence suggests that BRCA1 protein is involved in mammary carcinogenesis in sporadic and hereditary forms. Recent experimental results suggest that BRCA1 plays a role in the regulation of apoptosis. In order to test whether the analysis of human tumors would provide data supporting this hypothesis in sporadic breast carcinomas, we have investigated the relationship between BRCA1 and apoptosis-related genes. Immunohistochemical analysis was performed to determine BRCA1 and the apoptosis-related proteins bcl-2, Bax and p53 in paraffin-embedded tissues of 156 sporadic invasive ductal carcinomas. BRCA1 expression was positively-correlated with Bcl-2 expression (p = 0.0008), but no relationship between BRCA1 expression and Bax or p53 expression could be established. In addition, loss of BRCA1 expression was also related to poor tumor differentiation and lymph node metastasis. Our study shows that bcl-2 might be one of the target genes involved in the oncogenesis related to BRCA1. Loss of BRCA1 may contribute to tumor development in breast carcinomas, which may be independent of the p53 tumor suppressor.
Yang
Qifeng
Q
Second Department of Pathology, Department of Surgery, Affiliated Kihoku Hospital, Wakayama Medical University, Wakayama, Japan. yang-qf@mail.wakayama-med.ac.jp
Yoshimura
Goro
G
Nakamura
Misa
M
Nakamura
Yasushi
Y
Suzuma
Takaomi
T
Umemura
Teiji
T
Mori
Ichiro
I
Sakurai
Takeo
T
Kakudo
Kennichi
K
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019313:BRCA1 Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein