Abstract 4738: Androgen regulation of HER3 in prostate cancer differs by duration of treatment

Abstract Background: Prostate cancer (PCa) is the second most common cause of cancer-related death in men and occurs in 1 out of every 8 men. Normal prostate and PCa are responsive to androgens. The interplay between androgens and the ERBB3/HER3 receptor tyrosine kinase has recently been shown to differ by race. ERBB3 was higher in Black/African American patients and correlated with the androgen response pathway despite stable expression of the androgen receptor (AR) transcript. HER3 protein expression was negatively correlated with intraprostatic androgen in Black/African American men. Here we examined the effects of androgen dose and treatment duration on the HER3 pathway in vitro. Methods: Three PCa cell lines were used; MDA-PCa-2b, derived from an African American patient bone metastasis, LNCaP and LaPC4 derived from white patient lymph nodes. Cells were treated for 48h or 6 months with low or high dose R1881 (synthetic androgen). Endpoints include proliferation (Incucyte), gene expression (RT-qPCR), and protein levels (Western blot). Neuregulin (NRG1) was used to stimulate the HER3 pathway. Results: PCa treated for 48h with R1881 showed a biphasic effect on proliferation, whereas those treated for 6 months showed a dose-dependent increase. HER3 protein levels were increased after 48h of R1881 but decreased during the 6-month exposure. NRG1 treatment slightly increased cell proliferation. Ongoing experiments will examine NRG1 signaling in the R1881-treated cell lines. Conclusions: The crosstalk between the HER3 pathway and androgens, two key pathways known to drive aggressive prostate cancer, has been shown to play a more pronounced role in PCa in African American men compared to their White counterparts. Moreover, short-term exposures in vitro may not mimic the effects of androgens in vivo. Citation Format: Reem Belal Zalloum, Robert A. Holt, John Smetana, Candice Loitz, Lillian Perez, Larisa Nonn. Androgen regulation of HER3 in prostate cancer differs by duration of treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4738.