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KMID : 0869720020130010093
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Lung Research Institute
2002 Volume.13 No. 1 p.93 ~ p.103
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Alteration of cell growth and morphology by overexpression of transforming growth factor β type Ⅱ receptor in human lung adenocarcinoma cells
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Young Whan Kim/Tae Kyun Kim
Eun Kyung Mo/Chul Gyu Yoo/Choon Taek Lee/Sung Koo Han/Young Soo Shim/Young Whan Kim
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Abstract
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TGF-β is a potent inhibitory regulator of cell growth, which is transduced through interaction between type I (RI) and type II (RII) receptors that form heteromeric kinase complexes. Abnormal expression of these receptors has been identified in several human epithelial cancers and has been shown to be highly associated with resistance to TGF-β. In this study, we investigated the expression of RI and RII in 13 human non-small cell lung cancer cell lines (NSCLCs) and demonstrated decreased or loss of RII expression in five lung cancer cell lines, but not of RI. Of these cell lines, the role of RII in NCI-H358 adenocarcinoma, which lacks RII and is insensitive to TGF-β, was investigated by transducing this cell line with a recombinant retrovirus expressing full-length TGF-β RII. Stably transfected cells showed significant increase in RII mRNA and protein expression. These cells responded to exogenous TGF-β1 with suppressed proliferation in a dose-dependent manner and G1 arrest accompanied by morphological change distinct from control cells. We also investigated whether overexpression of dominant-negative RII (dnRII) in NCI-H441 adenocarcinoma, which is sensitive but expresses low levels of RII, could block signaling through the receptor complex. The overexpression of this kinase-domain-truncated RII by expressing the retroviral dnRII construct led to loss of the ability to respond to TGF-β1 and an exhibition of uncontrolled growth. These results suggest a close association between the loss of the expression of wild-type TGF-β RII and carcinogenesis in human lung cancer cells.
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KEYWORD
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TGF-β, TGF-β receptor, Dominant-negative, Carcinogenesis, Rb protein, Cyclin A, Lung cancer,
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