Rhomboid domain containing 2 (RHBDD2): A novel cancer-related gene over-expressed in breast cancer

Autor: Ezequiel Lacunza, María Virginia Croce, Amada Segal-Eiras, Claudio M Aldaz, Maria I. Nunez, Martín Carlos Abba, Andrea G. Colussi, Marina T. Isla-Larrain
Rok vydání: 2009
Předmět:
gene amplification
DNA Mutational Analysis
Breast cancer
0302 clinical medicine
Gene duplication
Gene expression
Breast
skin and connective tissue diseases
Regulation of gene expression
0303 health sciences
Serine Endopeptidases
Prognosis
Immunohistochemistry
Neoplasm Proteins
3. Good health
Gene Expression Regulation
Neoplastic
Isoenzymes
Gene Knockdown Techniques
030220 oncology & carcinogenesis
gene expression profile
Molecular Medicine
Female
Molecular Sequence Data
Breast Neoplasms
Biology
Article
03 medical and health sciences
breast cancer
Cell Line
Tumor
Biomarkers
Tumor
medicine
Humans
Gene silencing
Gene Silencing
RNA
Messenger
Molecular Biology
Cell Proliferation
030304 developmental biology
Gene amplification
Base Sequence
Gene Expression Profiling
Membrane Proteins
Cancer
Epithelial Cells
Gene expression profile
medicine.disease
Molecular biology
Gene expression profiling
Alternative Splicing
RHBDD2
Ciencias Médicas
Follow-Up Studies
Zdroj: CIC Digital (CICBA)
Comisión de Investigaciones Científicas de la Provincia de Buenos Aires
instacron:CICBA
SEDICI (UNLP)
Universidad Nacional de La Plata
instacron:UNLP
ISSN: 0925-4439
DOI: 10.1016/j.bbadis.2009.07.006
Popis: 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.
Facultad de Ciencias Médicas
Databáze: OpenAIRE
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