Author:
Liu Yongzhong,Gao Lingqiu,Gelman Irwin H
Abstract
Abstract
Background
SSeCKS is a major protein kinase C substrate with kinase scaffolding and metastasis-suppressor activity whose expression is severely downregulated in Src- and Ras-transformed fibroblast and epithelial cells and in human prostate, breast, and gastric cancers. We previously used NIH3T3 cells with tetracycline-regulated SSeCKS expression plus a temperature-sensitive v-Src allele to show that SSeCKS re-expression inhibited parameters of v-Src-induced oncogenic growth without attenuating in vivo Src kinase activity.
Methods
We use cDNA microarrays and semi-quantitative RT-PCR analysis to identify changes in gene expression correlating with i) SSeCKS expression in the absence of v-Src activity, ii) activation of v-Src activity alone, and iii) SSeCKS re-expression in the presence of active v-Src.
Results
SSeCKS re-expression resulted in the attenuation of critical Src-induced proliferative and pro-angiogenic gene expression including Afp, Hif-1α, Cdc20a and Pdgfr-β, and conversely, SSeCKS induced several cell cycle regulatory genes such as Ptpn11, Gadd45a, Ptplad1, Cdkn2d (p19), and Rbbp7.
Conclusion
Our data provide further evidence that SSeCKS can suppress Src-induced oncogenesis by modulating gene expression downstream of Src kinase activity.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference74 articles.
1. Lin X, Nelson PJ, Frankfort B, Tombler E, Johnson R, Gelman IH: Isolation and characterization of a novel mitogenic regulatory gene, 322, which is transcriptionally suppressed in cells transformed by src and ras. Mol Cell Biol. 1995, 15: 2754-2762.
2. Nauert J, Klauck T, Langeberg LK, Scott JD: Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffolding protein. Current Biology. 1997, 7: 52-62.
3. Gordon T, Grove B, Loftus JC, O'Toole T, McMillan R, Lindstrom J, Ginsberg MH: Molecular cloning and prelimnary characteriztion of a novel cytoplasmic antigen recognized by myasthenia gravis sera. J Clin Invest. 1992, 90: 992-999.
4. Xia W, Unger P, Miller L, Nelson J, Gelman IH: The src-suppressed C kinase substrate, SSeCKS, is a potential metastasis inhibitor in prostate cancer. Cancer Res. 2001, 15: 5644-5651.
5. Gelman IH: The role of the SSeCKS/Gravin/AKAP12 scaffolding proteins in the spaciotemporal control of signaling pathways in oncogenesis and development. Front Biosci. 2002, 7: 1797-
Cited by
26 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献