Interferon-α and -γ inhibit the growth and neoplastic potential of V- src-transformed human epithelial cells by reducing SRC tyrosine kinase activity
✍ Scribed by Hiromitsu Fujishima; Shuji Nakano; Takashi Tatsumoto; Naoko Masumoto; Yoshiyuki Niho
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 271 KB
- Volume
- 76
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
To investigate whether interferons (IFNs) selectively suppress the growth of solid tumor cells with elevated protein tyrosine kinase (PTK) activity, we evaluated the effect of recombinant IFN-␣2a and IFN-␥ on the proliferative and neoplastic potentials triggered by p60 v-src using v-src-transformed HAG-1 human epithelial cells. When compared with control cells harboring the pSV2neo gene, the monolayer growth of v-src-transformed cell lines was inhibited by both recombinant IFNs, in a dose-dependent manner, whereas growth of ras-transfected cell lines was not affected. Moreover, IFNs markedly reduced the clonogenic growth of v-srctransformed cells in soft-agar rather than monolayer growth, suggesting the preferential activity of IFNs on anchorageindependent growth. Pretreatment of cells with Src or the Src-like PTK inhibitor herbimycin A or radicicol, alleviated dose-dependently the growth-inhibitory activity of IFN-␣2a against v-src-transformed cells, suggesting that IFNs may share a common inhibitory pathway with Src PTK inhibitors. Accordingly, like herbimycin A, IFNs were found to reduce tyrosine phosphorylation of p60 v-src and suppressed in vitro p60 v-src kinase activity in v-src-transformed cells. Our data, together with the fact that IFNs inhibit the growth potential driven by Src but not by activated Ras, suggest that inhibition of signal transduction pathway through Src to downstream transduction events may be a primary mechanism of IFNinduced anti-prolifeative and anti-tumoral activity. Int.