Basic research of gene targeting and molecular targeting therapy for relapse of prostate cancer

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Since it is not clear why advanced prostate cancer relapses during hormone therapy, we established androgen-independent prostate cancer, LNCaP-SF and LN-REC4 cells from androgen-sensitive cell line, LNCaP. We characterized these cell lines in order to investigate what kinds of mechanisms are involved in progression. LNCaP-SF cells proliferation was stimulated in the absence of androgen and repressed in the presence of androgen. It was suggested that LN-REC4 induced angiogenesis. Now we are investigating the genes which are differentially regulated by androgen.We also succeeded in establishment of osteoblastic metastatic model of prostate cancer using LNCaP-SF cells. Osteoclast showed important role in osteoblastic metastasis of prostate cancer cells, and we certified that the 3rd generation of bisphosphonates could inhibit osteoblastic bone metastasis as well as osteolytic bone metastasis of prostatic cancer. through inhibition of osteoclast. Furthermore, bisphosphonates not only showed indirect action through osteoclast but also directly induced apoptosis of cancer cells and inhibited invasion through repression of chemokine receptor, CXCR-4 expression. These results indicate that the 3rd generation of bisphosphonates has potency of bone metastasis preventive medicine for prostate cancer.For development of molecular target drug for oncogene Her-2 assumed that the expression is enhanced in recrudescence prostatic cancer, we also used Her-2 specific-tyrosine kinase inhibitor and confirmed the antitumor effect in vitro and in vivo.