Abstract 3259: TGFβ signaling is frequently attenuated in hepatocellular carcinomas but is retained for malignant phenotypes in some hepatocellular carcinoma cells

• Published in: Cancer research (Chicago, Ill.) Vol. 72; no. 8_Supplement; p. 3259
• Main Authors: Mu, Xiaoxin, Herzig, Maryanne C., Washburn, William K., Walter, Christi A., Halff, Glenn A., Sun, Lu-Zhe
• Format: Journal Article
• Language: English
• Published: 15.04.2012
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-3259

Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Its development and progression have been shown to be regulated by various cytokines including TGFβ. However, the role of TGFβ signaling in the progression of HCC remains controversial. In the current study, we examined the expression levels of TGFβ pathway components and the activation status of Smad2/3 proteins as reflected by phospho-Smad2/3 levels in human and mouse HCC tissues and human HCC cell lines. We also investigated whether abrogation of TGFβ signaling in HCC cell lines that are responsive to TGFβ affects the growth and metastasis of transplanted HCC cells in nude mice. Quantitative real-time RT-PCR and Western immune blotting analyses reveal widespread down-regulation of TGFβ signaling pathway components including Smad2/3 and TGFβ type I and II receptors in HCC tissues of patients and mice in comparison to adjacent normal tissues. Treatment of our HCC cell lines (SNU398, SNU423, HepG2, and Sk-Hep-1) with TGFβ1 revealed that the SNU398 cell line was refractory whereas the other three cell lines were sensitive to TGFβ as determined with a number of in vitro assays including Smad phosphorylation, gene transcription, and growth inhibition assays. Knockdown of TGFβ type II receptor with shRNA significantly reduced TGFβ signaling activity in the Sk-Hep-1 cell line resulting in suppressed growth of its subcutaneous tumors and reduced metastasis potential when the cells were inoculated through tail vein injection. Our results suggest that TGFβ signaling may play a suppressive role in early stage of HCC development, but a promoting role in advanced stage, which is represented by the Sk-Hep-1 cell model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3259. doi:1538-7445.AM2012-3259