Contradicting the positive association reported in previous studies, our results indicate that R-Ras activation may negatively regulate the transformation of breast epithelial cells, and the loss of activation of R-Ras may be involved in the carcinogenesis of breast cancer.
All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis.
Recent studies have found that high level of p23 may promote tumor progression and poor prognosis in breast cancer patients. p23 was found to be overexpressed in our previous microarray assay of 100 childhood acute lymphoblastic leukemia (ALL) bone marrow (BM) samples.
High nuclear p23 was found to be associated with high cytoplasmic p23, therefore both may promote tumor progression and poor prognosis by increasing metastatic potential and drug resistance in breast cancer patients.
Consequently, it is important not to dismiss the Ras pathway in the development of breast cancer merely because of the infrequent detection of mutations in ras itself, but rather to consider the influence of aberrations upstream or downstream of Ras and of certain Ras-related proteins in the development of breast cancer.