Abstract 3131: IGF-I regulates Cyr61-induced breast cancer cell growth and migration

Abstract

Abstract Cysteine-rich 61 (Cyr61) is a protein involved in wound healing, regulation of extracellular matrix microenvironment, and in tumor invasion. Data from our laboratory and others have shown that highly invasive cancer cells have high Cyr61 transcriptional levels as compared with non-invasive cells. Recent studies from our laboratory have shown that IGF-I (insulin growth factor I) is involved in activating the PI3/Akt pathway, and this may increase Cyr61 expression. We have hypothesized that IGF-I induces tumor invasion by upregulating Cyr61 through Akt phosphorylation (pAkt). In the current study, several breast cancer cell lines, MDA-MB231, BT474, MCF-7, SKBR3 were used; two of which were stably transfected with active Akt1(SKBR3/AA and MCF-7/AA) and dominant negative Akt1 (SKBR3/DN and MCF-7/DN). To determine Cyr61 expression in response to IGF-I, cells were treated with IGF-I and Cyr61 expression was examined by RT-Real time PCR. To determine cell invasiveness in relation to Cyr61 expressions and IGF-I induction, a migration assay was used. Our result showed that Cyr61 expression was significantly higher in MDA-MB231 cells. SKBR3/AA and MCF-7/AA had increased levels of Cyr61, while SKBR3/DN and MCF-7/DN had decreased levels of Cyr61 compared to SKBR3 and MCF-7. Furthermore, IGF-I (100ng/ml) increased Cyr61 expression significantly and cells with high level of Cyr61 increased invasiveness. In summary, active Akt was associated with the IGF-I induced Cyr61, which caused breast cancer cell migration and invasion. Hence, Cyr61 may be a potential therapeutic target for treatment of invasive breast tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3131.