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Title: Analysis of androgen-independence in cell models of advanced prostate cancer
Author: Grant, Ewan Stewart
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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The expression of the androgen receptor gene in cell models of prostatic epithelia and its relationship with the apoptosis inhibiting oncogene bcl-2 was examined. The inability of the metastatic prostate cancer cell lines DU145 and PC3 to respond to androgens is well documented. However, the LNCaP cell line displays marked growth stimulation in the presence of the androgen dihydrotestosterone (DHT) at concentrations between 0.001nM and 10.0nM. Paradoxically, LNCaP demonstrate growth stimulation in the presence of the non-steroidal anti-androgen hydroxy-flutamide with significant (p<0.05) effects being observed at concentrations of 1.0mM and 10.0nM 4days post-administration. Primary cultures of prostatic epithelial cells derived from both benign hyperplastic (BPH) prostates and from prostate cancer (CaP) tissues, in common with DU145 and PC3, do not exhibit growth response to either DHT or to hydroxy-flutamide at any of the concentrations employed. Northern analysis of total RNA samples, using a 1kb PCR probe complementary to the 3' portion of the androgen receptor (AR) cDNA, demonstrates that of all the cells examined only the LNCaP cell line displays detectable AR gene transcripts. Increasing the sensitivity of AR mRNA detection through the use of reverse transcription-polymerase chain reaction (RT-PCR) enables detection of AR gene expression in LNCaP, PC3 and both BPH-derived and CaP-derived primary epithelial cells. In contrast RT-PCR, coupled with Southern blotting, was unable to identify AR mRNA in the DU145 cell line. This apparent complete down-regulation of AR gene expression cannot be blamed on any gross rearrangements or deletions within the gene since all 8 exons were detectable by PCR.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available