SSeCKS-Gravin-AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesisReportar como inadecuado

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BMC Cancer

, 6:105

First Online: 25 April 2006Received: 24 January 2006Accepted: 25 April 2006DOI: 10.1186-1471-2407-6-105

Cite this article as: Liu, Y., Gao, L. & Gelman, I.H. BMC Cancer 2006 6: 105. doi:10.1186-1471-2407-6-105


BackgroundSSeCKS 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.

MethodsWe 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.

ResultsSSeCKS 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.

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

AbbreviationsSSeCKSSrc Suppressed C Kinase Substrate

PKCprotein kinase C

RT-PCRreverse transcription-polymerase chain reaction

VEGFvascular endothelial growth factor

PTpermissive temperature

NPTnon-permissive temperature

PAbpolyclonal antibody

MAbmonoclonal antibody



Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-6-105 contains supplementary material, which is available to authorized users.

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Autor: Yongzhong Liu - Lingqiu Gao - Irwin H Gelman


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