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Over-Expression of Aryl Hydrocarbon Receptor (AhR) Enhances Src Kinase Activity to Functionally Induce AR Signaling and Promote Prostate Cancer Progression

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.

Identiferoai:union.ndltd.org:auctr.edu/oai:digitalcommons.auctr.edu:cauetds-1244
Date21 May 2018
CreatorsGhotbaddini, Maryam
PublisherDigitalCommons@Robert W. Woodruff Library, Atlanta University Center
Source SetsAtlanta University Center
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceElectronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

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