It is well documented that African-American (AA) patients present with more advanced states of breast cancer (BC) and have lower survival rates than Caucasian-Americans (CA). Some of this disparity is due to socioeconomic factors;however interaction of social and environmental factors can also modulate biological factors. A classic example is the protective effect that lactation has in preventing breast cancer in women. Several studies have shown how social factors, race, ethnic differences and socioeconomic status affect initiation, frequency, and duration of breastfeeding practices of mothers. These factors also affect a mother's decision whether or not to breastfeed and for how long she will breastfeed. Epidemiological data have shown that pregnancy and lactation at early age in humans reduces the risk of breast cancer. Nevertheless, the mechanism of this protective effect in humans is unknown. Studies in mice and rats have shown that lactation stimulates the expression of intracellular fatty-acid binding proteins (FABPs). Different FABPs (1-9) are expressed in specific tissues such as heart, brain, liver, etc. FABP3 expression is significantly increased in breast tissue of lactating rats and its expression regulates the protective effect initiated by lactation. FABP3 is also detected in human breast tissue and it is known as mammary-derived growth inhibitor (MDGI) because it has a strong inhibitory effect on cell proliferation. Well established is also the fact that FABPs have a compensatory relationship, i.e., levels of x-FABP increase when y-FABP is decreased. Therefore, since FABP3 inhibits breast cell proliferation, we reasoned that differential expression of this protein in breast tissues will correlate with breast cancer progression. Thus, we hypothesize that AA women will have lower levels of FABP3 since lactation rates among AA women are the lowest among CA, Hispanic (HA) and Asian American women. Similarly, we reasoned that FABP5 levels (also detected in breast) will be higher in tissues from AA women to compensate for the decrease in FABP3. Therefore we propose to assess the expression of these FABPs in paired normal/tumor BC tissues from AA and CA (obtained from Human Cooperative Tissue Network) to determine if lower expression of FABP3/higher expression of FABP5 among AA women is associated with the disparity in BC progression observed between AA and CA BC patients. To characterize the potential mechanisms associated with the regulation of FABP3 and FABP5 we will also use cell lines established from CA and AA patients obtained from ATCC. Protein levels of FABPs will be assessed by Western blotting, Elisa Assays and confocal immunofluorescence. mRNA levels will be assessed by quantitative rt-PCR. Since lactation is regulated by prolactin and IGF-II, we will also determine how these proteins regulate FABPs and cellular differentiation of the BC cell lines established from AA and CA women. If successful, our studies will provide much needed information about the mechanisms involved in the protective effect lactation induces in the breast and will potentially offer new tools for preventive breast cancer treatment.
Breast cancer is second only to lung cancer in terms of cancer-related death, and therefore, reducing the incidence of breast cancer is a critical health objective. African-American women have been shown to suffer from disproportionately high levels of breast cancer death compared to Caucasian women. In addition to socioeconomic concerns, biological factors such as differences in the expression of FABPs may contribute to this survival disparity. Our studies will provide much needed information about the mechanisms involved in the protective effect lactation induces in the breast and will potentially offer new tools for preventive breast cancer treatment.
