[Development of anti cancer drugs targeted on Fas-mediated apoptosis signal].
The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) is, in part, executed by inducing apoptosis through the cell surface antigen Fas on the target cells. There are many cancer cells that resist Fas-mediated apoptosis. To elucidate the mechanism of this resistance is very important to understand the process of tumor development. We focused on FAP-1 (Fas-associated phos phatase-1), a negative regulator of Fas-mediated apoptosis. The expression of FAP-1 was detected in many colon cancer cell lines. On the other hand no FAP-1 expression was detected in the normal colon tissue. We have found that the tri-peptide of Fas C-terminus inhibited the binding of Fas and FAP-1 in vitro. Microinjection of the tri peptide (Ac SLV) could induce Fas-mediated apoptosis in the DLD 1 human colon cancer cell line that was resistant to anti-Fas-antibody. These findings suggest that the interaction of Fas and FAP-1 has a very important role in Fas-mediated apoptosis signal transduction. The inhibition of the Fas/ FAP-1 binding will provide a good target to develop anti-cancer drugs.
Takahashi
M
M
Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd.
Kataoka
S
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D000970:Antineoplastic Agents; D019014:fas Receptor; D017027:Protein Tyrosine Phosphatases