SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis.

BMC Cancer
Yongzhong LiuI H Gelman

Abstract

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. 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. 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. Our data provide further evidence that SSeCKS can suppress Src-induced oncogenesis by modulating gene expression downstream of Src kinase activity.

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Citations

Dec 6, 2012·Experimental Hematology & Oncology·Hosam A ElbazCerasela Zoica Dinu
May 28, 2013·The American Journal of Pathology·Olatz CrendeFernando Vidal-Vanaclocha
Jun 23, 2010·International Journal of Cancer. Journal International Du Cancer·Yahao BuIrwin H Gelman
Mar 30, 2017·Nature Communications·Vasavi SundaramTing Wang
Sep 14, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Thomas WeissmüllerSean P Colgan
Jun 5, 2019·Acta Physiologica·Peter M BenzIngrid Fleming
Aug 21, 2012·Journal of Proteome Research·Nicole P ChappellThomas P Conrads
Jun 17, 2008·Biochemical and Biophysical Research Communications·Moon-Chang ChoiYung-Jue Bang

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Methods Mentioned

BETA
chips
chip
PCR
GTPase
GTPases

Software Mentioned

SAM
Data Mining Tool
GeneTraffic Uno
GeneTools
dChip
GeneSpring

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