TY - JOUR
T1 - Rhomboid domain containing 2 (RHBDD2)
T2 - A novel cancer-related gene over-expressed in breast cancer
AU - Abba, M. C.
AU - Lacunza, E.
AU - Nunez, M. I.
AU - Colussi, A.
AU - Isla-Larrain, M.
AU - Segal-Eiras, A.
AU - Croce, M. V.
AU - Aldaz, C. M.
N1 - Funding Information:
The authors gratefully acknowledge Dr Aysegul Sahin (Department of Pathology, MD Anderson Cancer Center, Houston — TX), who kindly provided some breast cancer samples; and John Ludes-Meyers for help with the western-blot. This work was supported by FONCYT (PICT N°32702, BID 1728 OC/AR), CONICET (PIP N°112-200801-02131), and NIH-NCI (1U19 CA84978-1A1) grants.
PY - 2009/10
Y1 - 2009/10
N2 - 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 cancer cell 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 breast carcinomas. 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.
AB - 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 cancer cell 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 breast carcinomas. 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.
KW - Breast cancer
KW - Gene amplification
KW - Gene expression profile
KW - RHBDD2
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U2 - 10.1016/j.bbadis.2009.07.006
DO - 10.1016/j.bbadis.2009.07.006
M3 - Article
C2 - 19616622
AN - SCOPUS:70349270573
SN - 0925-4439
VL - 1792
SP - 988
EP - 997
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 10
ER -