ABSTRACT
BACKGROUND: Bax is one of the main effectors of apoptosis in breast cancer. However, in contrast with the antiapoptotic protein Bcl-2, which has been extensively studied in this tumor, there are relatively few clinical studies on the biological role of Bax in breast cancer. MATERIALS AND METHODS: The expression of the apoptosis-related Bax gene was studied in a series of 255 previously untreated breast cancers by means of immuno-flow cytometry. Additionally, and by the same method, the expression of the Bcl-2, VEGF and Nup88 genes were also studied. As variables of the study for the final statistical analysis, the histological variety of the tumors, histological and nuclear grade, the expression of hormone receptors, p53, Ki-67 or c-erb-B2, axillary node invasion, tumor size and DNA-ploidy were also included. RESULTS: The expression of the proapoptotic Bax protein was significantly associated with the expression of Nup88 (p<0.0001), VEGF (p=0.0014) and Bcl-2 (p=0.0063), all measured by the same method. An inverse correlation with c-erb-B2 expression, which almost attained statistical significance (p=0.058) was also registered. CONCLUSION: This study adds evidence to the little explored link between apoptosis and angiogenesis. Furthermore, it discloses a previously unreported relationship between Bax and Nup88 expression.
Subject(s)
Breast Neoplasms/metabolism , bcl-2-Associated X Protein/biosynthesis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/metabolism , Flow Cytometry , Humans , Immunohistochemistry , Neoplasm Staging , Nuclear Pore Complex Proteins/biosynthesis , Nuclear Pore Complex Proteins/genetics , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/genetics , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor A/genetics , bcl-2-Associated X Protein/geneticsABSTRACT
BACKGROUND: There are very few studies on the final triggers of apoptosis, the caspases, in breast cancer. MATERIALS AND METHODS: Caspase-3 expression was studied by means of reverse transcript polymerase chain reaction (RT-PCR) in a series of 108 previously untreated patients with breast cancer. Expression levels were correlated with those obtained using the same technique of the apoptosis-associated X-chromosome genes RBMX, RBM3, RBM10 small and RBM10 large variant; Bcl-2 and Bax; the angiogenesis-associated genes VEGF and CD105 (endoglin); hMAM and Nup88. The correlation with the expression of hormone receptors, c-erb-B2, mutant p53 and Ki-67, all measured by means of immunohistochemistry, was also studied, as well as that with standard clinical parameters such as histological type, tumor size, axillary metastasis and DNA-ploidy. RESULTS: The only statistically significant correlations observed between caspase-3 mRNA expression and the parameters tested were a direct one with both the Bax (p = 0.007) and the small variant of the X-chromosome RBM10 gene (p = 0.018), and an inverse one with the angiogenesis-associated CD105 (endoglin) gene (p = 0.044). CONCLUSION: These results indicate that very few genes are involved in the last steps of the apoptotic cascade in breast cancer, among them one of the X-chromosome RBM family. They also support the relatively unexplored link between apoptosis and angiogenesis.
