A novel regulation of PSMA and PSA expression by Q640X AR in 22Rv1 and LNCaP prostate cancer cells

Abstract

We have investigated the expression of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) transcripts in androgen-dependent (LNCaP) and androgen-independent (22Rv1) prostate cancer cell lines. We also enquired whether Q640X CTE-truncated androgen receptor (AR) has an impact on transcription of mRNA for PSMA and PSA in transfected androgen-sensitive prostate cancer LNCaP cells. Wild type LNCaP, 22Rv1 prostate cancer cells, prostate stromal cells (PrSC) and LNCaP cells transfected with p-Q640X AR, p-WT AR or p-C3 empty plasmids were studied. The expression of PSMA and PSA were detected by real-time PCR after transfection for 4 and 7 days. Expression of mRNAs for PSA was sixfold greater than PSMA in wild type LNCaP cells. In contrast, the wild type androgen refractory 22Rv1 cell line reacted almost exactly the opposite way reverse to LNCaP cells, since the transcription of mRNA for PSMA almost twofold greater than PSA. Non-transfected human PrSC responded similarly to PSMA mRNA and PSA mRNA was not detected in these cells. Q640X AR transfected LNCaP cells downregulated the expression of PSMA and PSA genes after 7 days. Our results demonstrate that Q640X mutated AR may have an important regulatory role in mediating the PSMA and PSA genes expression during the progression of prostate cancer from androgen-dependence to androgen-independence. Understanding their functional properties and mechanisms by which ARs involved in regulation of PSMA and PSA expression will allow the identification of new target therapies for the treatment of hormone-resistant prostate cancer.

Establishment of an orthotopic prostate cancer xenograft mouse model using microscope-guided orthotopic injection of LNCaP cells into the dorsal lobe of the mouse prostate

“…In the present study, orthotopic prostate tumors stained positive for AR, PSA, and P504S and were p63 negative. These data imply that the orthotopic LNCaP xenograft mouse model is an excellent tool to investigate the molecular mechanisms of prostate cancer progression [3].…”

“…The LNCaP cell line constitutes androgen receptorpositive prostate cancer cells that express prostatespecific antigen (PSA) and prostate specific membrane antigen (PSMA), a marker of disease aggressiveness [3]. Subcutaneous and orthotopic LNCaP xenograft animal models closely mimic the progression of androgendependent prostate cancer in humans.…”

Roles of Progesterone, Testosterone and Their Nuclear Receptors in Central Nervous System Myelination and Remyelination

“…In contrast, testosterone can be metabolized by the aromatase to estradiol (E2) [70,[125][126][127]. Mutations in the AR can lead to several diseases in humans such as cancer, Kennedy's disease (spinal and bulbar muscular atrophy) and complete androgen insensitivity syndrome (CAIS) [128][129][130]. Several mutations of AR have been described.…”

Preparation of Doxorubicin-Retinoic Acid Hip Complex Nanomicellar Formulation for Doxorubicin Delivery to Prostate Cancer

“…DOX-RA loaded pentablock nanomicellar formulation was incubated with Prostate cancer PC-3 cells for 12 h and 24 h under conducive conditions of 5% carbon dioxide, 37 o C (30). An appropriate media for the growth of the cells was used [30][31][32]. Cells were incubated in chamber slides with pentablock nanomicelles bearing DOX-RA complex [33,34].…”