INVESTIGADORES
ABBA Martin Carlos
artículos
Título:
The human rhomboid domain containing 2 (RHBDD2): a novel cancer-related gene amplified and overexpressed in invasive breast carcinomas.
Autor/es:
ABBA MC; LACUNZA E; NUNEZ MI; COLUSSI A; ISLA-LARRAIN M; SAHIN A; SEGAL-EIRAS A; CROCE MV; ALDAZ CM
Revista:
BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE
Editorial:
Elsevier
Referencias:
Año: 2009 vol. 1792 p. 988 - 997
ISSN:
0925-4439
Resumen:
In the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified RHBDD2 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 RHBDD2 alternatively spliced mRNA isoforms expressed in breast cancercell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting RHBDD2 in 131 breast samples. RHBDD2 gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no RHBDD2 amplification was detected in normal breast tissues (n=17) or breast benign lesions (n=16) (p=0.014). Interestingly, siRNA-mediated silencing of RHBDD2 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 RHBDD2 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 breastcarcinomas. In conclusion, our findings suggest that RHBDD2 over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression.
