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J Surg Res. 2010 Jun 1;161(1):76-82. doi: 10.1016/j.jss.2008.10.031. Epub 2008 Nov 29.

Id1/Id3 knockdown inhibits metastatic potential of pancreatic cancer.

Author information

  • 1Department of Surgical Oncology, University of Tokyo, Tokyo, Japan. shuu@tkg.att.ne.jp

Abstract

BACKGROUND:

The Id (inhibitor of DNA binding/differentiation) proteins belong to the helix-loop-helix transcriptional regulatory factors, and play important roles in tumor development. Previously, we and others have shown that targeting Id in tumor cells could have important clinical implications. In the present study, we aimed to evaluate the effects of Id inhibition in human pancreatic cancer cells.

MATERIALS AND METHODS:

Id1 and Id3 were stably double-knockdown in human pancreatic cancer cell line MIA-Paca2 by means of RNA interference. Expression of Id and integrins were analyzed by flow-cytometry. Cell proliferation was evaluated by MTS assay. Migration was measured by wound closure assay. Adhesion assay was performed to evaluate binding capacity for different extracellular matrix proteins. Finally, in vivo properties of tumor cells were observed in a mouse model of peritoneal metastasis.

RESULTS:

Id1/Id3 double-knockdown resulted in decreased ability of pancreatic cancer cells to proliferate and migrate. In addition, Id1/Id3 double-knockdown caused decreased expression of integrins alpha3, alpha6, and beta1, and consequently reduced adhesion of tumor cells to laminin. Finally, peritoneal metastases of Id1/Id3 double-knockdown tumor cells were significantly reduced.

CONCLUSIONS:

We concluded that the Id proteins play a pivotal role in the development of peritoneal metastasis of pancreatic cancer, and consequently, their targeting would be a novel strategy for the prevention and treatment of pancreatic cancer.

Copyright (c) 2010 Elsevier Inc. All rights reserved.

PMID:
19515385
[PubMed - indexed for MEDLINE]
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