Id-1 promotes proliferation of p53-deficient esophageal cancer cells.

Abstract

The helix-loop-helix protein inhibitor of differentiation and DNA binding (Id-1) is known to promote cellular proliferation in several types of human cancer. Although it has been reported that Id-1 is over-expressed in esophageal squamous cell carcinoma (ESCC), its function and signaling pathways in esophageal cancer are unknown. In our study, we investigated the direct effects of Id-1 on esophageal cancer cell growth by transfecting an Id-1 expression vector into an ESCC cell line (HKESC-3), which showed serum-dependent Id-1 expression. Ectopic Id-1 expression resulted in increased serum-independent cell growth and G1-S phase transition, as well as up-regulation of mouse double minute 2 (MDM2) and down-regulation of p21Waf1/Cip1 protein expressions in the transfectant clones in a p53-independent manner. However, overexpression of Id-1 had no effect on the pRB, CDK4 and p16INK4A expressions. Stable transfection of Id-1 antisense expression vector to inhibit the expression of endogenous Id-1 in another ESCC cell line (HKESC-1) reversed the effects on MDM2 and p21Waf1/Cip1. In addition, Id-1 expression protected ESCC cells from Tumor Necrosis Factor (TNF)-alpha-induced apoptosis by up-regulating and activating Bcl-2. In conclusion, our study provides evidence for the first time that Id-1 plays a role in both proliferation and survival of esophageal cancer cells. Our findings also suggest that unlike prostate, hepatocellular and nasopharyngeal carcinomas in which Id-1 induces cell proliferation through inactivation of p16INK4A/RB pathway, the increased cell proliferation observed in ESCC cells may be mediated through a different mechanism.

• Authors: Cheuk Man Hui, Pak Yan Cheung, Ming Tat Ling, Sai Wah Tsao, Xianghong Wang, Yong Chuan Wong, Annie L M Cheung
• Journal: International journal of cancer (Int J Cancer) Vol. 119 Issue 3 Pg. 508-14 (Aug 01 2006) ISSN: 0020-7136 [Print] United States
• PMID: 16506209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2006 Wiley-Liss, Inc.

Chemical References

• CDKN1A protein, human
• Culture Media
• Culture Media, Serum-Free
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p21
• DNA, Antisense
• ID1 protein, human
• Inhibitor of Differentiation Protein 1
• Retinoblastoma Protein
• Tumor Suppressor Protein p53
• MDM2 protein, human
• Proto-Oncogene Proteins c-mdm2

Topics

• Blotting, Western
• Carcinoma, Squamous Cell (genetics, metabolism, pathology)
• Cell Cycle (physiology)
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival (physiology)
• Culture Media (pharmacology)
• Culture Media, Serum-Free (pharmacology)
• Cyclin-Dependent Kinase Inhibitor p16 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• DNA, Antisense (genetics)
• Esophageal Neoplasms (genetics, metabolism, pathology)
• Gene Expression (drug effects)
• Humans
• Inhibitor of Differentiation Protein 1 (genetics, metabolism, physiology)
• Proto-Oncogene Proteins c-mdm2 (metabolism)
• Retinoblastoma Protein (metabolism)
• Signal Transduction (physiology)
• Transfection
• Tumor Suppressor Protein p53 (deficiency, metabolism)