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SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis.
- Source :
-
BMC cancer [BMC Cancer] 2006 Apr 25; Vol. 6, pp. 105. Date of Electronic Publication: 2006 Apr 25. - Publication Year :
- 2006
-
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.<br />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.<br />Results: SSeCKS re-expression resulted in the attenuation of critical Src-induced proliferative and pro-angiogenic gene expression including Afp, Hif-1alpha, Cdc20a and Pdgfr-beta, and conversely, SSeCKS induced several cell cycle regulatory genes such as Ptpn11, Gadd45a, Ptplad1, Cdkn2d (p19), and Rbbp7.<br />Conclusion: Our data provide further evidence that SSeCKS can suppress Src-induced oncogenesis by modulating gene expression downstream of Src kinase activity.
- Subjects :
- A Kinase Anchor Proteins
Angiogenic Proteins biosynthesis
Angiogenic Proteins genetics
Animals
Cell Cycle Proteins biosynthesis
Cell Cycle Proteins genetics
Cell Division genetics
DNA, Complementary genetics
Gene Expression Profiling
Genes, src
Mice
NIH 3T3 Cells metabolism
Neovascularization, Physiologic genetics
Oligonucleotide Array Sequence Analysis
Rats
Recombinant Fusion Proteins physiology
Reverse Transcriptase Polymerase Chain Reaction
Cell Cycle Proteins physiology
Gene Expression Regulation, Neoplastic genetics
Oncogene Protein pp60(v-src) physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 16638134
- Full Text :
- https://doi.org/10.1186/1471-2407-6-105