PSA regulates androgen receptor expression in prostate cancer cells
Authors
Saxena, ParmitaTrerotola, Marco
Wang, Tao
Li, Jing
Sayeed, Aejaz
Vanoudenhove, Jennifer
Adams, Dave S.
Fitzgerald, Thomas J.
Altieri, Dario C.
Languino, Lucia R.
UMass Chan Affiliations
Department of Cancer Biology, Department of Radiation Oncology,Document Type
Journal ArticlePublication Date
2012-05-15Keywords
Cell Line, TumorDown-Regulation
Humans
Male
Metribolone
Neoplasms, Hormone-Dependent
Phosphorylation
Prostate-Specific Antigen
Prostatic Neoplasms
Proto-Oncogene Proteins pp60(c-src)
Receptors, Androgen
Neoplasms
Oncology
Metadata
Show full item recordAbstract
BACKGROUND: Prostate-specific antigen (PSA) is a pivotal downstream target gene of the androgen receptor (AR), and a serum biomarker to monitor prostate cancer (PrCa) progression. It has been reported that PSA transactivates AR, but the mechanistic requirements of this response have not been investigated. METHODS: We studied the localization of PSA, AR, and Src in intracellular compartments of synthetic androgen (R1881)-stimulated LNCaP and C4-2B PrCa cells, using immunofluorescence and subcellular fractionation approaches. We also investigated the effect of downregulation of PSA on AR expression by immunoblotting and real-time PCR using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Src activity was analyzed by immunoblotting. RESULTS: R1881 stimulation induced nuclear localization of both PSA and AR in LNCaP and C4-2B PrCa cells as well as increased phosphorylation of Src. Stable shRNA or transient siRNA knockdown of PSA resulted in reduced AR protein levels as well as AR mRNA levels in C4-2B cells. Similar to C4-2B cells, ablation of AR levels upon silencing of PSA was also confirmed in VCaP cells, another androgen-independent cell line. Silencing of PSA did not cause significant changes in Src activation; besides, Src regulation by integrins did not appear to affect AR transcriptional activity. CONCLUSIONS: PSA localizes to nuclei of androgen-stimulated PrCa cells, and controls AR mRNA and protein levels. This regulatory loop is specific for PSA, does not involve known AR activators such as Src and AKT, and may contribute to AR signaling under conditions of increasing PSA levels in patients.Source
Prostate. 2012 May 15;72(7):769-76. doi: 10.1002/pros.21482. Epub 2011 Sep 28. Link to article on publisher's siteDOI
10.1002/pros.21482Permanent Link to this Item
http://hdl.handle.net/20.500.14038/47935PubMed ID
21956655Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/pros.21482