Rational Derivatives of Maspin as Candidate Tumor Suppressive Agents of Breast Cancer
Abstract
We proposed to generate and characterize six rational derivatives of maspin as candidate tumor suppressive agents of breast cancer. We plan to produce these novel maspin variants as purified proteins (Specific Objective 1), and as re-expressed proteins in breast tumor cells that are transfected with the corresponding coding cDNAs (Specific Objective 2). The biological functions of these six maspin derivatives as well as the wild type maspin will be examined using comprehensive cellular and biochemical as says that have been established in my laboratory. In particular, I will focus on the effect of these molecules on tumor growth, cell adhesion, cell motility and invasion. In addition the biochemical and biophysical properties of these new molecules will be evaluated. Our unexpected results prompted a new investigation of the role of maspin in breast tumor progression. To further explore the clinical application of maspin in human cancer, it is critical to understand the in vivo biological function of maspin in tumor progression. To this end, one of the most powerful models used to examine multistage carcinogenesis has been MMTV/TGF-alpha; transgenic mouse. Elevated levels of TGF-alpha; have been detected in transformed keratinocytes and in a variety of naturally occurring human tumor types (Gottlieb, 1988; Reddy, 1994). In addition, the role of TGF-alpha; in neoplasia has been confirmed in a variety of experimental systems, including transgenic mice in which initially hyperplasia and later neoplasia of liver and mammary glands were observed (Thappan, 1990; Matsui, 1990; Sandgren, 1990). In collaboration with Dr. Kaladhar Reddy at WSU, we evaluated the role of maspin as a tumor suppressor using MMTV/TGF-alpha; transgenic mouse model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA405530
Entities
People
- Shihie Sheng
Organizations
- Wayne State University