The Role of SHP1 as a Tumor Suppressor Gene in Human Mammary Turmorigenesis.
Abstract
SHPl is a cytosolic protein tyrosine phosphatase containing two SH2 domains. It is highly expressed in hematopoietic cells and at lower levels in epithelium. We introduced SHPl, both in its wild type (wt) or a catalytic inactive (dn) form, into the human breast cancer cell line MDA-MB23 1, where SHP 1 expression is nearly lost. The overexpression of wt SHP1, but not dn SHPl, led to enhanced anchorage- independent growth, as well as enhanced tumorigenicity, without altering cellular proliferation rate. Our results suggest that such an enhancement in tumorigenicity is not caused by increased angiogenesis. The overexpression of SHP 1 does not affect the magnitude of EGF signaling in the MDA-MB23 1 cell, but rather affect the duration of signaling. The overexpression of SHPl in the MDA-MB23 1 cells led to an average 15% increase in 60/01 phase population during cell cycle and a corresponding drop in S phase. SHP overexpression in this cell dine did not lead to any increase in Src protein tyrosine kinase activity. A study is underway to identity a potential downstream effector of SHP1, which has a molecular weight of 40 kDa with a pI between 5.1 and 6.6.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA375235
Entities
People
- Chuan Gao
Organizations
- The University of Texas MD Anderson Cancer Center