Abstract B60: Role of MUC1 mucin in American Indian breast cancer health disparity.

Abstract

Abstract Introduction: Considerable breast cancer health disparity exists among different racial/ethnic populations and geographic locations. For unknown reasons, American Indian women of the Northern Plains have a greater incidence and higher death rate due to breast cancer than Caucasian women living in the same geographical region. Additionally, American Indian women living in the Northern Plains also have a much higher incidence and death rate due to breast cancer than American Indian women living elsewhere in the United States. To investigate the potential molecular basis for breast cancer health disparity, we have initiated a study to compare the expression profiles of cancer associated proteins on breast cancer cases from American Indian and Caucasian women living on the Northern Plains. One protein of interest, MUC1, a transmembrane mucin, is known to be overexpressed in breast cancer and nuclear localization of MUC1 can have downstream effects on cell signaling and increase oncogenic phenotypes. American Indian women are exposed to cigarette smoke at rates higher than Caucasian women; therefore, we are also assessing the prevalence of aryl hydrocarbon receptor (AhR) activation in breast cancer tissues. Cigarette compounds can activate the AhR pathway and induce the expression of a variety of genes, some of which are known to be oncogenic. Methods: We have examined the expression profiles of MUC1 in breast cancer tissue collected from American Indian (n=40) and Caucasian (n=60) women by immunohistochemical analysis. The staining was analyzed by experienced pathologists and scored according to intensity (0-4) and percent of cancer cells stained positive (0-4). A composite score was calculated by multiplying the scores of intensity and percent of cells stained. Tissues were categorized by modified Bloom-Richardson's histological grade and the mean composite scores were compared amongst American Indian and Caucasian groups. In vitro experiments have also been conducted to examine a potential link between the activation of AhR by cigarette smoke compounds and an increase in MUC1 expression or change in cellular localization. Results and Conclusions: A differential expression/localization pattern of MUC1 was observed in American Indian breast cancer samples compared to Caucasian samples. Grade 3 breast cancer samples obtained from American Indian women showed higher nuclear MUC1 staining compared to Caucasian samples. We have also observed that breast cancer cells aberrantly express AhR and have increased AhR activation as shown by nuclear localization. We also observed a lower amount of nuclear p53 and membrane β-catenin expression. This result correlates with previous data showing that MUC1 inhibits the expression of p53 and decreases membrane β-catenin. In vitro data suggests that exposure to BaP increases the nuclear localization of MUC1. In conclusion, breast cancer tissue from American Indian women has a different expression profile of MUC1 and this finding may help to explain the cancer health disparity. Further investigation of these differences may promote understanding of the etiological differences and may identify effective treatment strategies for breast cancer in American Indian women. Citation Format: Diane M. Maher, Emily Gaster, Phillip Stephenson, Michael Koch, Susan Eliason, Meena Jaggi, Subhash C. Chauhan. Role of MUC1 mucin in American Indian breast cancer health disparity. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B60.