| Autor: |
Jomgeow, Tanyarat, Oji, Yusuke, Tsuji, Naoko, Ikeda, Yoko, Ito, Ken, Tsuda, Asako, Nakazawa, Tsutomu, Tatsumi, Naoya, Sakaguchi, Nao, Takashima, Satoshi, Shirakata, Toshiaki, Nishida, Sumiyuki, Hosen, Naoki, Kawakami, Manabu, Tsuboi, Akihiro, Oka, Yoshihiro, Itoh, Kazuyuki, Sugiyama, Haruo |
| Předmět: |
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| Zdroj: |
Cancer Science; Apr2006, Vol. 97 Issue 4, p259-270, 12p, 2 Color Photographs, 11 Black and White Photographs, 1 Diagram, 1 Chart, 8 Graphs |
| Abstrakt: |
The wild-type Wilms’ tumor gene WT1 is overexpressed in human primary leukemia and in a wide variety of solid cancers. All of the four WT1 isoforms are expressed in primary cancers and each is considered to have a different function. However, the functions of each of the WT1 isoforms in cancer cells remain unclear. The present study demonstrated that constitutive expression of the WT1 17AA(–)/KTS(–) isoform induces morphological changes characterized by a small-sized cell shape in TYK-nu.CP-r (TYK) ovarian cancer cells. In the WT1 17AA(–)/KTS(–) isoform-transduced TYK cells, cell–substratum adhesion was suppressed, and cell migration and in vitro invasion were enhanced compared to that in mock vector-transduced TYK cells. Constitutive expression of the WT1 17AA(–)/KTS(–) isoform also induced morphological changes in five (one gastric, one esophageal, two breast and one fibrosarcoma) of eight cancer cell lines examined. No WT1 isoforms other than the WT1 17AA(–)/KTS(–) isoform induced the phenotypic changes. A decrease in α-actinin 1 and cofilin expression and an increase in gelsolin expression were observed in WT1 17AA(–)/KTS(–) isoform-transduced TYK cells. In contrast, co-expression of α-actinin 1 and cofilin or knockdown of gelsolin expression by small interfering RNA restored WT1 17AA(–)/KTS(–) isoform-transduced TYK cells to a phenotype that was comparable to that of the parent TYK cells. These results indicated that the WT1 17AA(–)/KTS(–) isoform exerted its oncogenic functions through modulation of cytoskeletal dynamics. The present results may provide a novel insight into the signaling pathway of the WT1 gene for its oncogenic functions. ( Cancer Sci 2006; 97: 259–270) [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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