(2) The c-erb B-2/neu protein was detected in both androgen-receptor-positive (LNCaP) and -negative (PC-3 and DU-145) human prostate cancer cell lines.
Androgen-induced inhibition of cell proliferation in an androgen-insensitive prostate cancer cell line (PC-3) transfected with a human androgen receptor complementary DNA.
Evidence coming from studies on AR in prostatic cancer highlights the possibility that AR structural alterations may have significance in tumor progression.
It is possible that analogous to an activated/altered growth factor receptor oncogene, codon 877 mutant AR with altered ligand binding may provide a selective growth advantage in the genesis of a subset of advanced prostate cancer.
We analyzed the androgen-receptor genes from samples of metastatic androgen-independent prostate cancers to determine whether mutations in the gene have a role in androgen independence.
We have identified a similar molecular mechanism in vivo for endocrine treatment failure in human prostate cancer which involves amplification of the androgen receptor (AR) gene.
In other cases, altered androgen receptor activity due to its mutation or altered expression may lead to pathology such as recurrence of prostate cancer due to development of androgen independence allowing tumor cell proliferation under androgen deprivation.
These data indicate that AR gene mutations occur commonly in advanced prostate cancers prior to endocrine treatment of disease and may contribute to altered androgen responsiveness of the tumors.
Here we shown that androgen promoted up-regulation of AR mRNA in two androgen-independent human prostate cancer cell lines, PC3 and DU145, when each was transfected with a human AR cDNA.
To further investigate structural abnormality of the AR in a large number of human prostate cancers, exons B-H encoding DNA-and hormone-binding domains were examined by single-strand conformation polymorphism analysis of polymerase chain reaction products and direct sequencing.