Accession Number:

ADA478662

Title:

Interaction Between Cry61 and avbeta3 in Breast Cancer: Role in Texan Resistance

Descriptive Note:

Final rept. 16 Aug 2006-17 Aug 2007

Corporate Author:

EVANSTON NORTHWESTERN HEALTHCARE RESEARCH INST IL

Personal Author(s):

Report Date:

2007-09-01

Pagination or Media Count:

13.0

Abstract:

The angiogenic factor Cyr61 also known as CCN1 plays a key role in both the maintenance and the enhancement of a malignant phenotype in breast cancer. Cyr61 is overexpressed in about 30 of triple negative breast carcinomas, whereas Cyr61 expression levels in normal breast tissues are negligible. Our recent studies showed that Cyr61 overexpression renders human breast cancer cells highly resistance to the microtubule-interfering agent paclitaxel Taxol, a current drug of choice for the treatment of metastatic breast cancer. We have confirmed that expression of alphavbeta3, a Cyr61 receptor, is markedly upregulated in breast cancer cells expressing alphavbeta3 Cyr61. Our most recent data demonstrate that functional blockade of with a synthetic chemical peptidomimetic based upon the the RGD Arg-Gly-Asp motif, is specifically cytotoxic towards Cyr61- overexpressing breast cancer. Pharmacological interference with the Cyr61 interaction restores Taxol efficacy, implying that a previously unrecognized Cyr61alphavbeta3 -driven cellular signaling actively modulates breast cancer cell growth, apoptosis and Chemosensitivity.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE