Accession Number:

ADA470604

Title:

Development of a Novel Therapeutic Paradigm Utilizing a Mammary Gland-Targeted, Bin-1 Knockout Mouse Model

Descriptive Note:

Annual rept. 14 Feb 2006-13 Feb 2007

Corporate Author:

LANKENAU INST OF MEDICAL RESEARCH WYNNEWOOD PA

Personal Author(s):

Report Date:

2007-03-01

Pagination or Media Count:

51.0

Abstract:

Evidence of loss or attenuation of the Bin 1 gene in human breast cancers has implicated Bin 1 as a tumor suppressor or negative modifier gene in mammary gland epithelial cells. We have discovered that Bin 1 loss can promote tumorigenesis through an immune escape mechanism. This correlates with the negative regulatory impact that we have found Bin 1 to exert on the important immunomodulatory enzyme indoleamine 2,3-dioxygenase IDO. Previously we have reported how in combination with certain chemotherapeutic agents inhibitors of IDO can be employed in a non-obvious therapeutic regimen to successfully treat pre-established autochthonous breast tumors in MMTV-Neu transgenic mice. During this reporting period we have obtained evidence in mouse models that IDO expressed in plasmacytoid dendritic cells that accumulate in the tumor draining lymph node may be the relevant mechanism of immune escape in breast cancers not direct expression of IDO in the tumor. We have further found that inhibiting IDO may not be an effective chemopreventive strategy for breast cancer but may be an effective strategy for suppressing breast cancer metastasis.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research
  • Organic Chemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE