Accession Number:

ADA433858

Title:

Rationale Design of Human Prolactin Receptor Antagonists for Breast Cancer Therapy

Descriptive Note:

Final addendum rept. 15 Sep 2003-14 Sep 2004

Corporate Author:

CLEMSON UNIV SC

Personal Author(s):

Report Date:

2004-10-01

Pagination or Media Count:

21.0

Abstract:

There were two specific tasks listed in the proposal i.e. development of hPRL-G129R as a PRL receptor antagonist and development of PRL BP as PRL sequester as potential breast cancer therapeutics. The conclusions from this project are that we have demonstrated that hPRL-G129R has promise to be used as a breast cancer therapeutic, but not hPRL-BP. We have found that hPRL-G129R is able to inhibit breast cancer cell proliferation via the induction of apoptosis. We further presented evidence that shows the mechanism of hPRL-G129R induced breast cancer cell apoptosis is through the regulation of Bcl-2Bax gene expression. Data obtained from mouse breast cancer model also support the notion that the inhibition of PRL activity in breast cancer will inhibit its growth. In addition, we explored the possibility of using hPRL- G129K as a targeting molecule by creating fusion molecules such as G129R-IL-2 and C129R-endostatin. During past year, we have published 2 manuscripts directly related to this subject. In summary, we have further demonstrated that hPRL-G129R is a true PRL receptor antagonist. Its anti-breast tumor effects were confirmed using both in vitro and in vivo assays.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE