Involvement of Tyrosine Phosphatses in Insulin Signaling and Apoptosis in Breast Cancer
Abstract
Breast cancer incidence is highest in caucasian women lowest in American Indian women but these trends are reversed for type 2 diabetes. We hypothesized that distinctions in insulin load and signaling may play a role in both diseases and investigated the role of a tyrosine phosphatase PTP1B previously reported to be a regulator of both insulin signaling and breast cancer. We noted that calcium flux into breast cancer cells suppressed tyrosine phosphorylation and induced partial proteolysis of PTP1B resulting in liberation of PTP1B from its membranous anchor. To investigate the role of the cytoplasmic form of PTP1B (tPTP1B) in breast cancer cells we expressed it and various mutants (phosphatase-dead substrate-trap) in breast cancer cells under control of an inducible promoter. Unexpectedly, tPTP1B did not suppress insulin signaling but targeted phosphorylated HER2 suppressing its signaling. Our results suggest that activation of PTP1B by its partial proteolysis targets HER2 an oncogene common in aggressive breast cancer and modulation of PTP1B proteolysis through calcium flux may be a unique approach in treatment or prevention of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA487233
Entities
People
- Nicholas J. Donato
Organizations
- The University of Texas MD Anderson Cancer Center