Tags

Type your tag names separated by a space and hit enter

Inability of transforming growth factor-beta to cause SnoN degradation leads to resistance to transforming growth factor-beta-induced growth arrest in esophageal cancer cells.
Cancer Res. 2005 Jun 01; 65(11):4782-8.CR

Abstract

It is well established that loss of a growth inhibitory response to transforming growth factor-beta (TGF-beta) is a common feature of epithelial cancers including esophageal cancer. However, the molecular basis for the abrogation of this key homeostatic mechanism is poorly understood. In esophageal cancer cell lines that are resistant to TGF-beta-induced growth inhibition, TGF-beta also fails to decrease transcription of c-myc despite the presence of functional signaling components. Consequently, to gain a better understanding of the mechanisms leading to resistance to TGF-beta-induced growth arrest, the basis for the inability to decrease c-myc transcription was investigated. Regardless of sensitivity to TGF-beta-induced growth arrest, TGF-beta enhanced the ability of Smad3-protein complexes to bind c-myc regulatory elements. However, in a growth inhibition-resistant esophageal cancer cell line, the Smad3-protein complexes contained the SnoN oncoprotein. Furthermore, in esophageal cancer cell lines that are resistant to TGF-beta-induced growth arrest, TGF-beta does not cause degradation of SnoN. Analyses of the effect of modulating SnoN expression in both growth inhibition-sensitive and growth inhibition-resistant cell lines showed that degradation of SnoN is a prerequisite for both TGF-beta-induced repression of c-myc transcription and growth arrest. The data indicate that SnoN-Smad3 complexes do not cause repression of c-myc transcription but rather prevent functionality of active repressor complexes. Thus, these studies reveal a novel mechanism for resistance to TGF-beta-induced growth inhibition in esophageal cancer, namely the failure to degrade SnoN. In addition, they show that SnoN can block TGF-beta repression of gene transcription.

Authors+Show Affiliations

Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond 23298-0678, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15930298

Citation

Edmiston, Jeffery S., et al. "Inability of Transforming Growth Factor-beta to Cause SnoN Degradation Leads to Resistance to Transforming Growth Factor-beta-induced Growth Arrest in Esophageal Cancer Cells." Cancer Research, vol. 65, no. 11, 2005, pp. 4782-8.
Edmiston JS, Yeudall WA, Chung TD, et al. Inability of transforming growth factor-beta to cause SnoN degradation leads to resistance to transforming growth factor-beta-induced growth arrest in esophageal cancer cells. Cancer Res. 2005;65(11):4782-8.
Edmiston, J. S., Yeudall, W. A., Chung, T. D., & Lebman, D. A. (2005). Inability of transforming growth factor-beta to cause SnoN degradation leads to resistance to transforming growth factor-beta-induced growth arrest in esophageal cancer cells. Cancer Research, 65(11), 4782-8.
Edmiston JS, et al. Inability of Transforming Growth Factor-beta to Cause SnoN Degradation Leads to Resistance to Transforming Growth Factor-beta-induced Growth Arrest in Esophageal Cancer Cells. Cancer Res. 2005 Jun 1;65(11):4782-8. PubMed PMID: 15930298.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inability of transforming growth factor-beta to cause SnoN degradation leads to resistance to transforming growth factor-beta-induced growth arrest in esophageal cancer cells. AU - Edmiston,Jeffery S, AU - Yeudall,W Andrew, AU - Chung,Theodore D, AU - Lebman,Deborah A, PY - 2005/6/3/pubmed PY - 2005/7/29/medline PY - 2005/6/3/entrez SP - 4782 EP - 8 JF - Cancer research JO - Cancer Res VL - 65 IS - 11 N2 - It is well established that loss of a growth inhibitory response to transforming growth factor-beta (TGF-beta) is a common feature of epithelial cancers including esophageal cancer. However, the molecular basis for the abrogation of this key homeostatic mechanism is poorly understood. In esophageal cancer cell lines that are resistant to TGF-beta-induced growth inhibition, TGF-beta also fails to decrease transcription of c-myc despite the presence of functional signaling components. Consequently, to gain a better understanding of the mechanisms leading to resistance to TGF-beta-induced growth arrest, the basis for the inability to decrease c-myc transcription was investigated. Regardless of sensitivity to TGF-beta-induced growth arrest, TGF-beta enhanced the ability of Smad3-protein complexes to bind c-myc regulatory elements. However, in a growth inhibition-resistant esophageal cancer cell line, the Smad3-protein complexes contained the SnoN oncoprotein. Furthermore, in esophageal cancer cell lines that are resistant to TGF-beta-induced growth arrest, TGF-beta does not cause degradation of SnoN. Analyses of the effect of modulating SnoN expression in both growth inhibition-sensitive and growth inhibition-resistant cell lines showed that degradation of SnoN is a prerequisite for both TGF-beta-induced repression of c-myc transcription and growth arrest. The data indicate that SnoN-Smad3 complexes do not cause repression of c-myc transcription but rather prevent functionality of active repressor complexes. Thus, these studies reveal a novel mechanism for resistance to TGF-beta-induced growth inhibition in esophageal cancer, namely the failure to degrade SnoN. In addition, they show that SnoN can block TGF-beta repression of gene transcription. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15930298/Inability_of_transforming_growth_factor_beta_to_cause_SnoN_degradation_leads_to_resistance_to_transforming_growth_factor_beta_induced_growth_arrest_in_esophageal_cancer_cells_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15930298 DB - PRIME DP - Unbound Medicine ER -