Down-regulation of S-phase kinase associated protein 2 (Skp2) induces apoptosis in oral cancer cells.
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| Abstract |
S-phase kinase associated protein 2 (Skp2) is a member of an F-box family of substrate-recognition subunits of SCF ubiquitin-protein ligase complexes that has been implicated in the ubiquitin-mediated degradation of several key regulators of mammalian G1 progression, including the cyclin-dependent kinase inhibitor p27Kip1, a dosage-dependent tumor suppressor protein. The anti-sense effect was confirmed in two cell lines of oral cancer cells that also exhibited over-expression of the Skp2 protein. In this study, we examined the mechanism responsible for anti-sense-mediated growth inhibition of oral cancer cells in vitro and in vivo. Skp2-anti-sense treatment induced apoptosis characterized by an increase in the early apoptosis, fragmentation of nuclei and activation of caspase-3, -8 and -9. Moreover, the growth of xenograft tumors was markedly suppressed by Skp2-anti-sense treatment. Furthermore, histological specimen revealed apoptotic cell death was increased in Skp2-anti-sense treated tumors. Our results suggest that down-regulation of Skp2 appears to induce apoptosis in oral cancer cells, targeting this molecule could represent a promising new therapeutic approach for this type of cancer.
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| Authors | Koji Harada, Supriatno, Yuichiro Kawashima, Yasutaka Itashiki, Hideo Yoshida, Mitsunobu Sato |
| Journal | Oral oncology (Oral Oncol) Vol. 41 Issue 6 Pg. 623-30 (Jul 2005) ISSN: 1368-8375 [Print] England |
| PMID | 16050017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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