JunD, a member of the AP-1 family, is essential for cell proliferation in prostate cancer (PCa) cells. We recently demonstrated that JunD knock-down (KD) in PCa cells results in cell cycle arrest in G 1 -phase concomitant with a decrease in cyclin D1, Ki67, and c-MYC, but an increase in p21 levels. Furthermore, the over-expression of JunD significantly increased proliferation suggesting JunD regulation of genes required for cell cycle progression. Here, employing gene expression profiling, quantitative proteomics, and validation approaches, we demonstrate that JunD KD is associated with distinct gene and protein expression patterns. Comparative integrative analysis by Ingenuity Pathway Analysis (IPA) identified 1) cell cycle control/regulation as the top canonical pathway whose members exhibited a significant decrease in their expression following JunD KD including PRDX3, PEA15, KIF2C, and CDK2, and 2) JunD dependent genes are associated with cell proliferation, with MYC as the key downstream regulator. Conversely, JunD over-expression induced the expression of above genes including c-MYC. We conclude that JunD is a key regulator of cell cycle progression and inhibiting its target genes may be an effective approach to block prostate carcinogenesis.

Epidemiological studies show that the incidence and mortality rates of prostate cancer (PCa) are significantly higher in African-American (AA) men when compared with Caucasian (CA) men in the United States. Transforming growth factor β (TGFβ) signaling pathway is linked to health disparities in AAs. Recent studies suggest a role of TGFβ3 in cancer metastases and its effect on the migratory and invasive behavior; however, its role in PCa in AA men has not been studied. We determined the circulating levels of TGFβ3 in AA and CA men diagnosed with PCa using ELISA. We analyzed serum samples from both AA and CA men diagnosed with and without PCa. We show that AA PCa patients had higher levels of TGFβ3 protein compared with AA controls and CA patients. In fact, TGFβ3 protein levels in serum were higher in AA men without PCa compared with the CA population, which may correlate with more aggressive disease seen in AA men. Studies on AA-derived PCa cell lines revealed that TGFβ3 protein levels were also higher in these cells compared with CA-derived PCa cell lines. Our studies also reveal that TGFβ does not inhibit cell proliferation in AA-derived PCa cell lines, but it does induce migration and invasion through activation of PI3K pathway. We suggest that increased TGFβ3 levels are responsible for development of aggressive PCa in AA patients as a consequence of development of resistance to inhibitory effects of TGFβ on cell proliferation and induction of invasive metastatic behavior.

Research partnerships between universities and communities following the principles of community-based participatory research (CBPR) have the potential to eliminate cycles of health disparities. The purpose of this article is to describe the process of establishing a community-campus network with a distinct mission and vision of developing trusting and successful research partnerships that are sustained and effective. In 2019, Morgan CARES was established to facilitate community engagement by founding a community center “within” a low-income residential neighborhood as a safe and accessible hub for creating a vibrant learning community. A community needs assessment and asset mapping was conducted and several necessary resources and services were provided to maximize networking opportunities, nurture innovative ideas and proposals, and provide seed funding. Lessons learned informed the optimization of a theoretical model that has guided the development and implementation of the program’s key components. By December 2021, Morgan CARES had recruited 222 community and 137 academic members representing diverse expertise from across Baltimore City. We also successfully established new partnerships and funded a total of 17 small community-academic awards. Although in its early stages, Morgan CARES has established a dynamic learning community following a conceptual framework that could guide future similar initiatives.