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A novel dominant negative Smad2 mutation in a TGFbeta resistant human carcinoma cell line.
Anticancer Res. 2002 Jan-Feb; 22(1A):13-9.AR

Abstract

An important biological mechanism contributing to the transformed phenotype of cancer cells is the ability to escape normal growth regulatory signals. In epithelial cells, transforming growth factor beta (TGFbeta) inhibits cell cycle progression in the G1-phase. The abnormal ability of cancer cells to escape TGFbeta-induced cell cycle inhibition may lead to deregulated mitosis, providing a growth advantage to these clones. The effects of TGFbeta are mediated through type I and type II receptors, which are transmembrane proteins possessing cytoplasmic serine/threonine kinase domains for signal propagation. TGFbeta binds to the type II receptor which then phosphorylates the cytoplasmic domain of the type I receptor. The receptor complex recruits and phosphorylates the downstream signaling proteins, Smad2 and Smad3, which then associate with Smad4. The Smad complex translocates to the nucleus to regulate target gene expression resulting in cell cycle inhibition. We have identified a new Smad2 mutation in a TGFbeta-resistant human carcinoma line. The mutant Smad2 protein exhibits decreased association with the receptor complex, is not phosphorylated in response to TGFbeta, fails to associate with Smad4 and does not localize to the nucleus. Expression of the mutant Smad2 protein in a TGFbeta sensitive carcinoma line induces resistance to this growth inhibitory factor and deregulates TGFbeta-responsive gene expression. These results indicate that this novel Smad2 mutant protein has dominant negative activity in cultured cells.

Authors+Show Affiliations

Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles 90033, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12017275

Citation

Tsang, Kenneth J., et al. "A Novel Dominant Negative Smad2 Mutation in a TGFbeta Resistant Human Carcinoma Cell Line." Anticancer Research, vol. 22, no. 1A, 2002, pp. 13-9.
Tsang KJ, Tsang D, Brown TN, et al. A novel dominant negative Smad2 mutation in a TGFbeta resistant human carcinoma cell line. Anticancer Res. 2002;22(1A):13-9.
Tsang, K. J., Tsang, D., Brown, T. N., & Crowe, D. L. (2002). A novel dominant negative Smad2 mutation in a TGFbeta resistant human carcinoma cell line. Anticancer Research, 22(1A), 13-9.
Tsang KJ, et al. A Novel Dominant Negative Smad2 Mutation in a TGFbeta Resistant Human Carcinoma Cell Line. Anticancer Res. 2002 Jan-Feb;22(1A):13-9. PubMed PMID: 12017275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel dominant negative Smad2 mutation in a TGFbeta resistant human carcinoma cell line. AU - Tsang,Kenneth J, AU - Tsang,David, AU - Brown,Tamara N, AU - Crowe,David L, PY - 2002/5/23/pubmed PY - 2002/6/26/medline PY - 2002/5/23/entrez SP - 13 EP - 9 JF - Anticancer research JO - Anticancer Res VL - 22 IS - 1A N2 - An important biological mechanism contributing to the transformed phenotype of cancer cells is the ability to escape normal growth regulatory signals. In epithelial cells, transforming growth factor beta (TGFbeta) inhibits cell cycle progression in the G1-phase. The abnormal ability of cancer cells to escape TGFbeta-induced cell cycle inhibition may lead to deregulated mitosis, providing a growth advantage to these clones. The effects of TGFbeta are mediated through type I and type II receptors, which are transmembrane proteins possessing cytoplasmic serine/threonine kinase domains for signal propagation. TGFbeta binds to the type II receptor which then phosphorylates the cytoplasmic domain of the type I receptor. The receptor complex recruits and phosphorylates the downstream signaling proteins, Smad2 and Smad3, which then associate with Smad4. The Smad complex translocates to the nucleus to regulate target gene expression resulting in cell cycle inhibition. We have identified a new Smad2 mutation in a TGFbeta-resistant human carcinoma line. The mutant Smad2 protein exhibits decreased association with the receptor complex, is not phosphorylated in response to TGFbeta, fails to associate with Smad4 and does not localize to the nucleus. Expression of the mutant Smad2 protein in a TGFbeta sensitive carcinoma line induces resistance to this growth inhibitory factor and deregulates TGFbeta-responsive gene expression. These results indicate that this novel Smad2 mutant protein has dominant negative activity in cultured cells. SN - 0250-7005 UR - https://www.unboundmedicine.com/medline/citation/12017275/A_novel_dominant_negative_Smad2_mutation_in_a_TGFbeta_resistant_human_carcinoma_cell_line_ L2 - https://antibodies.cancer.gov/detail/CPTC-TGFB1-1 DB - PRIME DP - Unbound Medicine ER -