Androgen induces differentiation of a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line

Abstract

Androgen signaling is crucial for the growth and development, as well as for tumorigenesis of the prostate. However, many of the prostate epithelial cell lines developed previously, either normal or tumorigenic, do not express androgen receptor (AR) or respond to androgen. In order to advance our understanding on how androgen signaling regulates the growth and the differentiation status, and affects tumorigenicity of the epithelial cell, we performed experiments on HPr-1, a prostate cell line recently immortalized from normal human prostate epithelial cells. In the present study, AR was stably transfected into HPr-1 cells by replication-defective retrovirus. Treatment of HPr-1AR cells with androgen resulted in cell differentiation and growth retardation accompanied with up-regulation of cytokeratins K8 and K18, prostate specific antigen, p21 and p27, and down-regulation of c-myc, bcl-2 and telomerase activity. Our results suggest that androgen promotes the process of differentiation in a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line which may reflect the normal effects of androgen on prostate cells.

Cell- and gene-specific regulation of primary target genes by the androgen receptor

“…The HPr-1AR cell line, derived from immortalized normal human prostate epithelium, is androgen-responsive and expresses wild-type AR; androgen promotes differentiation of these cells, reminiscent of the normal actions of androgen on the prostate (Ling et al 2001). We treated HPr-1AR cultures with synthetic androgen R1881, or vehicle as a control, for 4, 8, 15, and 24 h, and identified androgen-regulated transcripts on spotted cDNA microarrays.…”

“…HPr-1AR cells, which express wild-type AR, were grown as described (Ling et al 2001) in keratinocyte serum free medium (Cat. # 17005-042, Invitrogen) and a 5% CO 2 atmosphere.…”

Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells

“…The androgen/AR roles in differentiation of prostate epithelium have been extensively studied (Ling et al 2001, Whitacre et al 2002, Garraway et al 2003, Berger et al 2004. When the AR gene was selectively knocked out in epithelial cells, the AR-deficient cells did not terminally differentiate (Simanainen et al 2007(Simanainen et al , 2009), which impedes prostate lobes' growth and function ).…”

Identification of a novel function of TWIST, a bHLH protein, in the development of acquired taxol resistance in human cancer cells

“…Preliminary experiments were conducted to ensure that the PCR conditions were at the logarithmic phase of the PCR reaction. The cDNA of b-actin was amplified as a control for the amount of cDNA present in each sample (primer details: sense: 5 0 -GTC GGG CGC CCC AGG CAC CA-3 0 , antisense: 5 0 -CTC CTT AAT GTC ACG CAC GAT TTC-3 0 ) (Ling et al, 2001). PCR products were electrophoresed on 2% agarose gels and were analysed using a gel documentation system (UltraViolet Product Limited, CA, USA).…”