Effects of the androgen receptor overexpression in prostate cancer
VARTIAINEN, PAULA (2007)
VARTIAINEN, PAULA
2007
Biokemia - Biochemistry
Lääketieteellinen tiedekunta - Faculty of Medicine
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Hyväksymispäivämäärä
2007-01-11
Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:uta-1-16520
https://urn.fi/urn:nbn:fi:uta-1-16520
Tiivistelmä
Background and aims: Prostate cancer is the leading cancer type in Finnish men. In about 30% of patients, the proceeding into a fatal hormone independent state involves the amplification and overexpression of the androgen receptor (AR) gene. The aim of the study was to find out, how the overexpression affects the proliferation of the cells in different circumstances and translocation to nucleus.
Methods: Two AR stabily overexpressing and two control LNCaP derived cell strains were used. The levels of AR expression were determined with qRT- PCR and Western blotting. The proliferation was studied with Coulter Counter and alamarBlue methods in different concentrations of dihydrotestosterone, R1881, and bicalutamide and in starvation conditions. The translocation process after androgen induction was studied with immunofluoresence staining.
Results: Expression of the AR in LN-AR E and C is about 3 4 and 11 15 fold in mRNA level and about 2 and 3 4 fold in protein level when compared to controls. The proliferation was greatest in 10 nM DHT and in 1 nM R1881. In starvation conditions, the proliferation of LN-AR C continued over three weeks. The effects of bicalutamide were controversial. The translocation process into nucleus occurred within an hour but back to cytoplasm in more than three hours. The intensity of the translocation correlated with the AR expression level in different cell strains.
Conclusions: The cell strains overexpressing AR are able to proliferate better in the absence and low concentrations of DHT and also translocate AR more efficiently when compared to controls.
Asiasanat: androgen receptor, overexpression, prostate cancer
Methods: Two AR stabily overexpressing and two control LNCaP derived cell strains were used. The levels of AR expression were determined with qRT- PCR and Western blotting. The proliferation was studied with Coulter Counter and alamarBlue methods in different concentrations of dihydrotestosterone, R1881, and bicalutamide and in starvation conditions. The translocation process after androgen induction was studied with immunofluoresence staining.
Results: Expression of the AR in LN-AR E and C is about 3 4 and 11 15 fold in mRNA level and about 2 and 3 4 fold in protein level when compared to controls. The proliferation was greatest in 10 nM DHT and in 1 nM R1881. In starvation conditions, the proliferation of LN-AR C continued over three weeks. The effects of bicalutamide were controversial. The translocation process into nucleus occurred within an hour but back to cytoplasm in more than three hours. The intensity of the translocation correlated with the AR expression level in different cell strains.
Conclusions: The cell strains overexpressing AR are able to proliferate better in the absence and low concentrations of DHT and also translocate AR more efficiently when compared to controls.
Asiasanat: androgen receptor, overexpression, prostate cancer