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Genetic integrity of transforming growth factor beta (TGF-beta) receptors in cervical carcinoma cell lines: Loss of growth sensitivity but conserved transcriptional response to TGF-beta

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Authors
Kang, Shin H.; Won, Kyungshick; Chung, Hwan‐Wook; Jong, Hyun‐Soon; Song, Yong‐Sang; Kim, Seong‐Jin; Bang, Yung‐Jue; Kim, Noe K.
Issue Date
1998-08
Citation
International Journal of Cancer, Vol.77 No.4, pp.620-625
Abstract
Transforming growth factor beta (TGF-beta) exerts an inhibitory effect on the growth of most epithelial cell types, and the loss of responsiveness to this growth inhibition has been implicated in the development of a variety of human cancers. The genetic alteration of TGF-beta receptors is known to play a critical role in this escape from growth regulation. We asked whether there is a correlation between TGF-beta sensitivity and the genetic status of TGF-beta type I and type II receptors (RI and RII, respectively) in human cervical carcinoma cell lines. Among 8 cell lines examined, 3 (ME-180, C-33A and HeLaS3) showed resistance to TGF-beta and 3 (SiHa, CaSki and HeLa229) showed minimal response to the growth inhibitory effect of TGF-beta; the other cell lines (HeLa and HT-3) were sensitive. Northern blot analysis revealed that the RII mRNA was not expressed in 2 TGF-beta-resistant cell lines (ME-180 and C-33A) but was expressed in the other cell lines. Southern blot analysis of RI and RII revealed a homozygous deletion of the entire TGF-beta RII gene in the cell line ME-180. We then asked whether the other TGF-beta-resistant or refractory cell lines had microsatellite instability and/or poly-adenine tract mutations of RII. We also checked for point mutations in the individual exons of the entire RII using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP). Although C-33A exhibited poly-adenine microsatellite instability, its RII gene showed no signs of mutation. The molecular integrity of the TGF-beta receptors in all cell lines, except ME-180 and C-33A, could be confirmed by examining the distinct transcriptional induction of plasminogen activator inhibitor-I (PAI-I), p21(WAFI/CIPI) and, in some cases, the accompanying downregulation of c-myc in response to TGF-beta. Our observations, taken together, indicate that inactivation of the RII contributes to the resistance to TGF-beta of some cervical carcinoma cell lines. Loss of or attenuated sensitivity to TGF-beta growth inhibition in other cells may be attributed to the disruption of distal components in the TGF-beta signal pathway, but not to the receptor system. Int. J. Cancer 77:620-625, 1998. (C) 1998 Wiley-Liss, Inc.
ISSN
0020-7136
URI
https://hdl.handle.net/10371/173110
DOI
https://doi.org/10.1002/(SICI)1097-0215(19980812)77:4<620::AID-IJC23>3.3.CO;2-5
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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