Abstract
Introduction: Health disparities among African American (AA) and Caucasian (CA) populations in the US constitute a major health problem that encompasses leading causes of morbidity and mortality such as breast cancer. AA women are more likely to have advanced disease at diagnosis, higher risk of recurrence and poorer prognosis than CA females. IGF-II is a potent mitogen that induces cell proliferation and survival signals through activation of the IGF-I (IGF-IR) and insulin (INSR) receptors, while the IGF2 receptor mediates IGF-II internalization for subsequent degradation. We hypothesize that differential expression of IGF-II and its associated receptors (INSR, IGFIR and IGF2R) between AA and CA women contributes to the health disparity observed between AA and CA women with breast cancer.
Methods: We examined IGF-II, INSR, IGF-IR and IGF2R mRNA and protein expression in paired breast tissue samples from AA and CA women by Real Time-PCR, western blot analysis and immunohistochemistry.
Results and Discussion: Our results showed significantly increased levels of INSR (isoforms A and B) mRNA in normal breast tissues from AA females than in normal tissues from CA women. IGFIR and IGF2R expression was higher in normal CA women. Furthermore, AA tumor samples expressed higher levels of INSR-A than CA tumor samples which showed higher levels of IGFIR, IGF2R and INSR-B. INSR protein expression was significantly higher in AA as compared to CA tissue samples.
Conclusion: We conclude that the differential expression of IGFIR, INSR and IGF2R between AA and CA females may contribute to the increased risk of breast fibrocystic disease and 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.
Second AACR International Conference on the Science of Cancer Health Disparities— Feb 3–6, 2009; Carefree, AZ
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