國家衛生研究院 NHRI:Item 3990099045/4720

NHRI > National Institute of Cancer Research > Neng-Yao Shih > Conference Papers/Meeting Abstract > Item 3990099045/4720

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4720

Title:	TGF-beta-induced Stat3 phosphorylation mediated growth regulation in lungi cancer
Authors:	Tseng, SW;Chen, KL;Ho, BY;Shih, NY
Contributors:	National Institute of Cancer Research
Abstract:	Background: Transforming growth factor-beta (TGFβ) is a well-known potent growth inhibitor for many tumor cells of epithelial origin. Loss of response to TGFβ-mediated growth inhibition is frequently associated with malignant progression in a variety of human cancers. However, during anticancer chemotherapy, tumor cells often develop a coordinate resistant to that drug and cytotoxic cytokines. Recent study has revealed the cross-resistance of adriamycin and TGFβ in tumor cells. However, no distinct mechanisms have been proposed. Thus, this study tried to dissect the relationship between acquisition of drug resistant of tumor cells and subsequent acquisition of resistance to TGFβ. Materials and methods: NCI-H23 parental (H23P) and NCI-H23 adriamycin resistant (H23ADR) lung adenocarcinoma cell lines were used in this study. The variations of biological functions induced by TGFI3 in these two cell lines were studied by cell proliferation assays, flow cytometric analyses, transcription reporter assays, and Western blotting. Results: We demonstrated that, after TGFβ1 treatment, H23ADR cells are much more refractory to TGFβ-mediated growth suppression than their parental (H23P) cells. The action is not either attributed to differential expression of TGFβ receptors, or involved in TGFβ1-induced cell cycle arrest and cell death between these two cell lines. By comparison studies on differential activations of TGF[Mnduced signaling molecules, we first demonstrate that TGFβ1 can augment endogenous Stat3 activity in H23P cells with slow kinetics, but barely affects on H23ADR cells. Transfection of constitutively active Stat3 into H23ADR cells led to growth suppression in the absence of TGFβ1 ; additionally, expression of dominant-negative Stat3 significantly rescued H23P cells from TGFβ1-mediated growth suppression. Conclusion: Our data suggest that modulation of Stat3 activity play a critical role in the TGFβ1-regulated cell growth during acquired adriamycin resistance, and provide the first evidence that Stat3 activity is involved in the cell growth suppression elicited by TGFβ1 in cancer cells.
Date:	2005-10
Relation:	EJC Supplements. 2005 Oct;3(2):52.
Link to:	http://dx.doi.org/10.1016/S1359-6349(05)80481-1
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000247564800163
Appears in Collections:	[Neng-Yao Shih] Conference Papers/Meeting Abstract [Szu-Wen Tseng(1997-2007)] Conference Papers/Meeting Abstract

Files in This Item:

File	Description	Size	Format
ISI000247564800163.pdf		143Kb	Adobe PDF	614	View/Open

Loading...