Rational Design of Human Prolactin Receptor Antagonists for Breast Cancer Therapy

Abstract

There were two specific tasks listed in the proposal (finishing cell proliferation as says and summarizing data and manuscript preparation) for the final year of this three-year project. Since we have completed a majority of the tasks related to this project in terms of development of a PRL antagonist, hPRL-G129R. Our focus of research in the past 12 month has been on (1) to further confirm the anti-tumor effects of hPRL-G129R in vivo; (2) to develop hPRL-Gl29R based, breast cancer specific therapeutics; and (3) to reach a conclusion on hPRL-BP project. We have demonstrated that hPRL-G129R is able to inhibit the growth of two human breast cancer cell xenografts in nude mice (manuscript attached) . In terms of designing hPRL-G129R based therapeutics, we have designed and demonstrated efficacy of dual functional protein (G129R-1L2, manuscript attached) . We have also generated preliminary results regarding G129R-PE40 (abstracts attached) . We further confirmed relationship between hPRL, hPRL-G129R and bcl-2 in multiple breast cancer cells (manuscript attached) . On the other hand, we have exhausted our attempts in terms of producing hPRL-BP. In summary, we have demonstrated that hPRL-G129R is a true PRL receptor antagonist. It's anti-breast tumor effects were confirmed using both in vitro and in vivo assays. We are currently conducting pre-clinical studies of hPRL-G129R and hope to launch clinical phase studies.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2002
Accession Number
ADA410901

Entities

People

  • Wen Y. Chen

Organizations

  • Clemson University

Tags

DTIC Thesaurus Topics

  • Body Weight
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemistry
  • Dna Microarrays
  • Endocrine Glands
  • Epithelial Cells
  • Gene Expression
  • Health Services
  • Lymphocytes
  • Neoplasms
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Medicine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Medical Imaging.
  • Systems Analysis and Design