The insulin-like growth factor 1 pathway is a potential therapeutic target for low-grade serous ovarian carcinoma

Erin R. King, Zhifei Zu, Yvonne T M Tsang, Michael T. Deavers, Anais Malpica, Samuel C. Mok, David M. Gershenson, Kwong Kwok Wong

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Objective: To validate the overexpression of insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) in low-grade serous ovarian carcinoma (SOC), and to investigate whether the IGF-1 pathway is a potential therapeutic target for low-grade SOC. Methods: Gene expression profiling was performed on serous borderline ovarian tumors (SBOTs) and low-grade SOC, and overexpression of IGF-1 in low-grade SOC was validated by RT-PCR and immunohistochemistry. The effect of exogenous IGF-1 on cell proliferation was determined in cell lines by cell proliferation assays, cell migration assays, and Western blot. Signaling pathways downstream of IGF-1 and the effects of the AKT inhibitor MK-2206 were investigated by Western blot analysis and by generating IGF-1R short hairpin RNA stable knockdown cell lines. Low- and high-grade cell lines were treated with the dual IGF-1R- and insulin receptor-directed tyrosine kinase inhibitor OSI-906, and cellular proliferation was measured. Results: mRNA analysis and immunostaining revealed significantly higher IGF-1 expression in low-grade SOCs than in SBOTs or high-grade SOCs. In response to exogenous treatment with IGF-1, low-grade cell lines exhibited more intense upregulation of phosphorylated AKT than did high-grade cell lines, an effect that was diminished with IGF-1R knockdown and MK-2206 treatment. Low-grade SOC cell lines were more sensitive to growth inhibition with OSI-906 than were high-grade cell lines. Conclusions: IGF-1 is overexpressed in low-grade SOCs compared with SBOTs and high-grade SOCs. Additionally, low-grade SOC cell lines were more responsive to IGF-1 stimulation and IGF-1R inhibition than were high-grade lines. The IGF-1 pathway is therefore a potential therapeutic target in low-grade SOC.

Original languageEnglish (US)
Pages (from-to)13-18
Number of pages6
JournalGynecologic oncology
Volume123
Issue number1
DOIs
StatePublished - Oct 2011

Keywords

  • Insulin receptor
  • Insulin-like growth factor
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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