Abstract
Prostate cancer represents one of the leading causes of morbidity and mortality of men worldwide. In precision medicine, tumors are screened for specific genetic alterations known as predictive markers for targeted therapy. In androgen-independent prostate cancer cells and in tissue samples of a prostate cancer patient treated with Goserelin, we identified the self-activating splice variant Rac1b. Importantly, the expression of Rac1b was sufficient to induce AR-dependent gene synthesis. We hypothesized that Rac1b antagonizes androgen depletion induced cancer cell death by blocking pro-apoptotic signalling pathways. In line with that selective knockdown of Rac1b or inhibition of Rac-dependent signalling pathways reinduced apoptosis in androgen-independent prostate cancer cells suggesting Rac1b inhibition as a potential novel therapeutic add on strategy against prostate cancer.
Highlights
Prostate cancer (PCa) is considered the second leading cause of cancer deaths of men in the western hemisphere [1]
In androgen-independent prostate cancer cells and in tissue samples of a prostate cancer patient treated with Goserelin, we identified the self-activating splice variant Rac1b
A major clinical challenge to this approach is posed by frequent development of androgen-independent castration-resistant prostate cancer (CRPC), which is associated with increased morbidity and poor prognosis
Summary
Prostate cancer (PCa) is considered the second leading cause of cancer deaths of men in the western hemisphere [1]. Androgen deprivation therapy (ADT) represents a well-established pharmacological strategy to prevent tumor growth by promoting apoptosis in tumor cells. To mirror the progression of human prostate tumors before and after androgen withdrawal, the androgen-controlled human PCa cell line LNCaP and its androgen-independent sub-line C4-2 serve as an effective model system to analyse the basis of androgen independence [2,3,4,5]. Small GTP-binding proteins of the Rho-family (Rho GTPases) have emerged as critical factors in driving tumorigenesis [6, 7]. They act as molecular switches cycling between a GTP-bound active and a GDP-
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
