In:
International Journal of Cancer, Wiley, Vol. 119, No. 3 ( 2006-08), p. 508-514
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 p21 Waf1/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 p16 INK4A 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 p21 Waf1/Cip1 . In addition, Id‐1 expression protected ESCC cells from Tumor Necrosis Factor (TNF)‐α‐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 p16 INK4A /RB pathway, the increased cell proliferation observed in ESCC cells may be mediated through a different mechanism. © 2006 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2006
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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