Abstract #4288: Differential insulin-like growth factor II (IGF-II) expression may impact breast cancer incidence and survival among African-American and Caucasian women

Breast cancer incidence and mortality in the US varies significantly according to race and ethnicity. African-American (AA) women have a lower overall incidence, are more likely to have advanced disease at diagnosis and have a higher risk of recurrence and poorer prognosis than Caucasian females, but the reasons for this disparity are not well understood. Insulin-like growth factor II (IGF-II) is a potent mitogen actively involved in normal development and breast cancer cell survival, in part, by regulating anti-apoptotic proteins through activation of the IGF-I and insulin receptors. IGF-II regulation is complex and occurs at both, the transcriptional level by the production of four mRNAs with different translational efficiencies, and post-transcriptionally through IGF-II mRNA binding proteins (IMPs) and natural IGF-II antisense. We hypothesize that IGF-II plays a role in the survival disparity observed among AA breast cancer patients by stimulating rapid tumor growth, inhibiting apoptosis and promoting metastasis. This study examines IGF-II, IMPs, IGF-II natural antisense and the anti-apoptotic proteins Bcl-2, Bcl-XL and survivin. Protein and mRNA expression in breast tissue samples from AA and CA women was analyzed by western blot analysis and Real Time-PCR. Our results showed no correlation between mRNA and protein levels of IGF-II in paired breast tissues from AA and CA women. IGF-II mRNA levels were significantly higher in normal AA women (AAN), while IGF-II protein (14-17 kDa IGF-II precursor form) was significantly increased in malignant tissues from AA women (AAM) as compared to CA women. Noteworthy, IGF-II protein levels were post-transcriptionally regulated. IMPs (IGF-II mRNA binding proteins that increase translation) were increased in tissues from AA as compared to CA women, while endogenous IGF-II antisense mRNA (reduced IGF-II translation) was higher in CA samples as compared to AA samples. Of significance, IGF-II protein expression correlated with Bcl-X_L and survivin expression in paired breast tissues similarly to our published studies in breast cancer cells were IGF-II regulates these antiapoptotic proteins. In summary, IGF-II differential expression among AA and CA patients may contribute to the higher incidence and more aggressive breast cancer phenotype seen in AA women and represents a potential target for new anti-cancer therapies.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4288.