Identifying the factors and signal pathways necessary for anchorage-independent growth of Ha-ras oncogene-transformed NIH/3T3 cells |
| |
Authors: | Chang Tsuey-Yu Tsai Wen-Jiuan Chou Chao-Kai Chow Nan-Haw Leu Tzeng-Horng Liu Hsiao-Sheng |
| |
Institution: | Department of Parasitology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC. |
| |
Abstract: | Ha-ras(Val 12) overexpression was positively correlated with colony formation by NIH/3T3 derivative "2-12" cells harboring an inducible Ha-ras(Val 12) transgene. The ras-farnesylation inhibitor, Lovastatin, completely suppressed colony formation at higher dosages. However, Ha-ras oncogene overexpression alone could not stimulate colony formation under serum-deprived conditions, suggesting that ras is required but not sufficient for supporting colony formation. Substituting cow colostrum (AC-2) for serum did not result in colony formation from 2-12 cells in soft agar, suggesting the colostrum lacked or contained insufficient amounts of factors that stimulate colony formation. Supplementation of AC-2-containing medium with growth factors, such as insulin-like growth factor-1 (IGF-1), partially restored the capability of anchorage-independent cell growth induced by Ha-ras overexpression. Consistently, antibodies specific for IGF-1 receptors only partially blocked colony formation from 2-12 cells. The data indicate that multiple factors, including IGF-1, are required for Ha-ras-dependent colony formation. Signal transduction studies revealed that, under Ha-ras overexpression conditions, IGF-1 utilizes phosphatidyl inositol 3-kinase and NF-kappaB to transduce colony formation-related signaling. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|