IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model.
Biochem Biophys Res Commun
; 436(4): 740-5, 2013 Jul 12.
Article
in En
| MEDLINE
| ID: mdl-23792093
ABSTRACT
Trastuzumab (Herceptin®) has demonstrated clinical potential in several types of HER2-overexpressing human cancers. However, primary and acquired resistance occurs in many HER2-positive patients with regimens. To investigate the possible mechanism of acquired therapeutic resistance to trastuzumab, we have developed a preclinical model of human ovarian cancer cells, SKOV3/T, with the distinctive feature of stronger carcinogenesis. The differences in gene expression between parental and the resistant cells were explored by microarray analysis, of which IGF-1R and HER3 were detected to be key molecules in action. Their correctness was validated by follow-up experiments of RT-PCR, shRNA-mediated knockdown, downstream signal activation, cell cycle distribution and survival. These results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
Cell Transformation, Neoplastic
/
Receptor, IGF Type 1
/
Receptor, ErbB-2
/
Cell Proliferation
/
Antibodies, Monoclonal, Humanized
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2013
Type:
Article
Affiliation country:
China