Inhibition of growth and increase of acid phosphatase by testosterone on androgen-independent murine prostatic cancer cells transfected with androgen receptor cDNA.
Most androgen-unresponsive prostatic cancer cells are found to lack androgen receptor (AR). To clarify the role of AR in the process of the progression from androgen-dependent to androgen-unresponsive tumor, the AR gene was transfected into an AR-negative rat prostatic cancer cell line CUB-II. AR-transfectant cells expressed AR mRNA and showed binding to R1881. AR was found in nuclei of AR-transfectant cells by histochemical examination. Therefore, AR-transfectant cells were considered to contain functional AR. The growth of AR-transfectant cells was markedly inhibited in culture in the presence of testosterone, and the effect of testosterone was reduced by simultaneous addition of flutamide. Moreover, tumors inoculated with AR-transfectant cells in male mice showed much slower growth than those in females. The tumors of AR-transfectant cells in mice consisted of slightly larger spindle-shaped cells when compared to those of CUB-II cells. Moreover, AR-transfectant cells contained a few polynuclear giant cells. Since CUB-II cells contained acid phosphatase (AcP) activity, the addition of testosterone in culture increased AcP activity of AR-transfectant cells. It is concluded that resumption of androgen-dependent processes reduces the growth rate accompanying changes of phenotype.
Suzuki
H
H
Department of Urology, School of Medicine, Chiba University, Japan.
Nihei
N
N
Sato
N
N
Ichikawa
T
T
Mizokami
A
A
Shimazaki
J
J
D000135:Acid Phosphatase / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary; D005260:Female; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D011944:Receptors, Androgen; D013739:Testosterone; D000135:Acid Phosphatase