Abstract
Purpose: African American men have almost twice the incidence and death rates related to prostate cancer compared to Caucasian men. Several studies have suggested that some of these differences may be attributed to the elevated expression of different genes. Recently, a new class of genetic regulators has emerged known as microRNAs. Many reports have found microRNAs to be implicated in cell growth, cell differentiation and the onset of many diseases including prostate cancer. To date, there are only three commercially available African American prostate cancer cell line models. We were able to establish five African American prostate cell lines, representing each stage of prostate cancer progression. With the help of these models, we sought out to investigate the difference of microRNA expression in African American and Caucasian prostate cancer.
Methods: We analyzed the expression of over 300 microRNAs in 11 African American and Caucasian cell lines utilizing DiscovArray microRNA Microarray Chip. Validations of the most significant miRNAs were done by qRT-PCR. Characterization of the microRNA was carried out by performing MTT assay, Flow Cytometry, Western Blot, and Imunoflourescence.
Results: We identified 15 microRNAs that were differentially expressed between the African American and Caucasian cell lines. Further validations led to the identification of miR-152 which is significantly expressed among both groups. MiR-152 is thought to be responsible for inhibiting DNA methyltransferase 1 (DNMT1). Our results showed that miR-152 reduced cellular proliferation in PC-3, DU-145 and LNCaP prostate cancer cell lines. In addition, miR-152 inhibited DNMT1 protein expression as well as initiated G2-M cell cycle arrest.
Conclusion: Validation of these results indicates a significant difference in microRNA expression between African American and Caucasian prostate cancer. Furthermore, these results suggest that microRNAs may play a role in the advance progression seen in prostate cancer in African Americans. These findings are currently being validated in African American and Caucasian tissue samples. Research supported by G12 RR03059-21A1(NIH/RCMI), and CA118623 (NIH/NCI).
Citation Format: Shaniece Crystal Theodore, Melissa Davis, Rhim Jhong, Timothy Turner, Clayton Yates. Profiling miR-152 expression in African American prostate cancer cell lines. [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 B38.
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