Rhomboid Domain Containing 2 : A Novel Cancer-Related Gene Over-Expressed In Breast Cancer
Résumé
In the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as () to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified mRNA and protein expression significantly elevated in breast carcinomas compared with normal breast samples as analyzed by SAGE (n=46) and immunohistochemistry (n=213). Interestingly, specimens displaying RHBDD2 over-expression were predominantly advanced stage III breast carcinomas (p=0.001). Western-blot, RT-PCR and cDNA sequencing analyses allowed us to identify two alternatively spliced mRNA isoforms expressed in breast cancer cell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting in 131 breast samples. gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no amplification was detected in normal breast tissues (n=17) or breast benign lesions (n=16) (p=0.014). Interestingly, siRNA mediated silencing of expression results in a decrease of MCF7 breast cancer cells proliferation compared with the corresponding controls (p=0.001). In addition, analysis of publicly available gene expression data showed a strong association between high expression and decreased overall survival (p=0.0023), relapse-free survival (p= 0.0013), and metastasis-free interval (p=0.006) in patients with primary ER-negative breast carcinomas. In conclusion, our findings suggest that over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression.
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