ABSTRACT
Breast cancer metastasis suppressor-1 (BRMS1) is a putative antimetastatic gene. However, results relating its expression to the prognosis of breast cancer are still controversial, and all studies carried out to date have failed to show a relationship between the expression of BRMS1 and axillary lymph node metastasis in breast cancer. It has been recently suggested that BRMS1 may exert its physiological role through the modulation of apoptosis. In order to test this hypothesis, we studied the expression of BRMS1 and genes known to be directly related with apoptosis in human breast carcinoma. The expression of mRNA corresponding to BRMS1, BCL2, BAX, CASP3 and the apoptosis-related X-chromosome RNA binding motif (RBM) genes (RBMX, RBM3, RBM10 small and large variant) was studied by means of differential RT-PCR in 94 samples obtained from previously untreated patients with breast carcinoma. A significant (p=0.03) inverse correlation between BRMS1 mRNA expression and expression of the mRNA corresponding to the large variant of the X-chromosome RBM10 gene was found. The degree of direct correlation with another member of the X-chromosome RBM gene family, RBMX, almost attained statistical significance (p=0.06). These results point towards a possible link between BRMS1 expression and apoptosis in human breast cancer through a relationship with the expression of genes belonging to the X-chromosome RBM family.
Subject(s)
Apoptosis/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Neoplasm Proteins/genetics , Caspase 3/genetics , Chromosomes, Human, X , Female , Gene Expression Regulation, Neoplastic , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Humans , Mitochondria/genetics , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger , RNA-Binding Proteins/genetics , Repressor Proteins , bcl-2-Associated X Protein/geneticsABSTRACT
BACKGROUND: BRMS1, recently identified in MDA-MB-435 breast cancer cells, seems to act as a potent antimetastatic gene in experimental tumor models. MATERIALS AND METHODS: To verify if BRMS1 exerts its action in a similar way in clinical tumors, BRMS1-mRNA expression was investigated in a series of 107 human breast carcinomas and correlated with the presence or not of axillary node metastases. Additionally, BRMS1 expression was correlated with all available clinical (histologic variety, histologic and nuclear grade) and biological parameters (ploidy, expression of Ki67, hormone receptors, c-erb-B2 and p53), as well as with the expression of hMAM- and Nup88-mRNA, previously shown by us to correlate with very low and very high aggressiveness of breast cancer, respectively. RESULTS: Down-regulation of BRMS1 expression in the tumors did not correlate with the presence of axillary node metastases. Furthermore, BRMS1 expression did not correlate with any other of the studied clinical or biological tumor parameters. CONCLUSION: In clinical breast cancers, down-regulation of BRMS1 expression seems not to mimic the very clear-cut antimetatstatic properties displayed in experimental tumor models.
ABSTRACT
BACKGROUND: A gene located on the q11.23 region of the male chromosome, RBMY, which plays a role in spermatogenesis, is down-regulated in testicular cancer. RBMY is a diverged X-Y shared gene. The corresponding X chromosome gene, RBMX, is located on Xq26. MATERIALS AND METHODS: We studied fresh tissues from 122 infiltrating breast cancers (99 ductal infiltrating, 19 lobular infiltrating and 4 tubular carcinomas) for the expression of RBMX by means of differential RT-PCR (reverse transcription-polymerase chain reaction), using beta-actin as an internal control and normalization standard. The obtained results were compared with all available clinical and molecular data of the studied tumors (estrogen and progesterone receptors (ER & PR), c-erb-B2, p53, Ki67, DNA-ploidy, Bcl-2, VEGF, CD105 (endoglin), histologic variety, histologic and nuclear grade and axillary node invasion). RESULTS: RBMX RT-PCR was successful in 120/122 instances. All 120 cases expressed RBMX. The only significant correlation found between RBMX expression and all the variables tested was an inverse one with CD105 (endoglin) mRNA-expression (r=-3063; p=0.0007). CONCLUSION: The X-chromosome RBMX gene is expressed in all breast cancers. The expression is inversely correlated with the expression of the angiogenesis-associated CD105 (endoglin) gene. The precise meaning of this association has still to be elucidated.
