Over-expression of Aryl Hydrocarbon Receptor (AHR) enhances src kinase activity to functionally induce ar signaling and promote prostate cancer progression, 2018

Ghotbaddini, Maryam

2010-2019

The aryl hydrocarbon receptor (AhR) has been reported to interact with multiple signaling pathways during prostate development including the androgen receptor. AhR was overexpressed in LNCaP using PLNCX2 retrovirus vector containing AhR cDNA to determine if ectopic overexpression induces castrate resistant phenotype. The highly overexpressed AhR clone illustrated further increase in transcriptional and promotor activity for AhR and AR compared to the moderately overexpressed AhR clone and control. Western blot analysis showed more AhR, AR, cSrc, and pSrc protein expression in clones. AhR overexpression was found to induce several biological properties such as migration, invasion, proliferation, and promotion of G1 to S phase during the cell cycle. Bicalutamide treatment had no effect on AR transcriptional activity in either clone, proving resistance to anti-androgen therapy. Our results confirm that overexpression of AhR induces constitutive activity and stimulates androgen receptor signaling. This suggests a role for AhR in the development of CRPC. KEY TERMS: Prostate cancer, Aryl Hydrocarbon Receptor (AhR), Androgen Receptor (AR), Src kinase, CRPC, Biology

text

application/pdf

2018-05-21

dissertation

Doctor of Philosophy (PhD)

Clark Atlanta University

Biological Science

Powell, JoAnn
Khan, Shafiq
Odero-Marah, Valerie

Clark Atlanta University

Georgia--Atlanta

http://hdl.handle.net/20.500.12322/cau.td:2018_ghotbaddini_maryam