Abstract 281: Insulin-like growth factor II differential activation of the IGF-1 and insulin receptors in African-American and Caucasian breast cancer tissues

African-American (AA) women with breast cancer are more likely to have advanced disease at diagnosis, higher risk of recurrence and poorer prognosis than Caucasian (CA) females.

Insulin-like growth factor- II (IGF-II) is a potent mitogen that induces cell proliferation and survival signals through activation of the IGF-I (IGF-IR), insulin (INSR) and hybrid receptors. We hypothesize that differential expression of the IGF1R and INSR isoforms (IR-A, IR-B) between AA and CA women potentiates IGF-II mitogenic effects, thus contributing to the health disparity observed between these ethnic groups. We examined IGF-II, IGF1R and INSR isoforms protein expression and phosphorylation in paired breast tissue samples from AA and CA women by western blot analysis, immunohistochemistry and ELISA techniques. IGF-II expression was significantly higher in AA cell lines and tissue samples when compared to Caucasians. Furthermore, significantly increased expression of IGF1R was observed in AA normal tissues as compared to CA normal tissues, while IGF1R expression was similar between AA normal and malignant tissues. Moreover, AA tumor samples expressed significantly lower levels of IR-B protein than CA tumor samples. IGF1R, INSR, IRS-1 and Shc phosphorylation were significantly higher in AA tumor samples. We conclude that the differential expression and phosphorylation of IGF-II, IGF1R and INSR between AA and CA females coupled with differential activation of downstream signaling pathways may contribute to the increased risk of malignant transformation seen in young AA females, and the more aggressive breast cancer phenotype observed among AA breast cancer patients and represent, along with IGF-II, potential therapeutic targets against health disparities in breast cancer.

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 281.