The Role of SHP1 as a Tumor Suppressor in Human Mammary Tumorigenesis

Abstract

SHP-1, the Src homology 2-containing protein tyrosine phosphotase 1, involves in the dephosphorylation of growth factor-receptors or non-receptor protein tyrosine kinases and serves as a negative regulator of proliferative signaling in cells. In addition, PI3K signaling pathway plays an important role in growth factor-mediated cell survival and proliferation. To investigate the regulation of PI3K signaling in malignant epithelial cells, we studied the interaction of SHP-1 with multiple mediators in the cascade, including PI3K, PTEN and AKT. In SKBr3 cells, we observed a growth factor-stimulation induced association of SHP-1 with PTEN. Further study revealed that binding of SHP-1 to PTEN was enhanced by LCK, a Src family tyrosine kinase, suggesting a tyrosine phosphorylation-mediated interaction between the two proteins. In order to investigate the regulation of SHP-1 on PTEN, we coexpressed wild type SHP-1 or inactive mutant SHP-1 with PTEN in cells.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2000
Accession Number
ADA410923

Entities

People

  • Muling Mao

Organizations

  • The University of Texas MD Anderson Cancer Center

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Enzymes
  • Epithelial Cells
  • Growth Factors
  • Kinases
  • Neoplasms
  • Ovarian Cancer
  • Peptide Growth Factors
  • Peptides
  • Phosphorylation
  • Proteins
  • Regulations
  • Regulators
  • Tyrosine

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.