SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis.
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-1alpha, Cdc20a and Pdgfr-beta, and conversely, SSeCKS induced several cell cycle regulatory genes such as Ptpn11, Gadd45a, Ptplad1, Cdkn2d (p19), and Rbbp7.


CONCLUSIONS
Our data provide further evidence that SSeCKS can suppress Src-induced oncogenesis by modulating gene expression downstream of Src kinase activity.
Liu
Yongzhong
Y
Mucosal Immunology Unit, National Institutes of Health, Bethesda, MD 20892, USA. yoliu@mail.nih.gov
Gao
Lingqiu
L
Gelman
Irwin H
IH
D054758:A Kinase Anchor Proteins; D042501:Angiogenic Proteins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016391:Genes, src; D051379:Mice; D041681:NIH 3T3 Cells / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D042501:Angiogenic Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D015688:Oncogene Protein pp60(v-src)