IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model

Journal Article · Fri Jul 12 00:00:00 EDT 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.06.030· OSTI ID:22239670

Jia, Yanhan ^[1]; Zhang, Yan ^[2]; Qiao, Chunxia; Liu, Guijun ^[3]; Zhao, Qing ^[3]; Zhou, Tingting; Chen, Guojiang ^[3]; Li, Yali ^[2]; Feng, Jiannan; Li, Yan ^[3]; Zhang, Qiuping ^[1]; Peng, Hui ^[3]

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1. Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071 (China)
2. Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China)
3. Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China)

Highlights: •We established trastuzumab-resistant cell line SKOV3/T. •SKOV3/T enhances proliferation and in vivo carcinogenesis. •IGF-1R and HER3 genes were up-regulated in SKOV3/T based on microarray analysis. •Targeting IGF-1R and/or HER3 inhibited the proliferation of SKOV3/T. •Therapies targeting IGF-1R and HER3 might be effective in ovarian cancer. -- 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.

• OSTI ID: 22239670
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 436, Issue 4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENESIS
CELL CYCLE
DRUGS
IN VIVO
NEOPLASMS
PATIENTS
POLYMERASE CHAIN REACTION
THERAPY