Protein tyrosine phosphatase-1B and T-cell protein tyrosine phosphatase regulate IGF-2-induced MCF-7 cell migration

Biochem Biophys Res Commun. 2010 Jan 29;392(1):83-8. doi: 10.1016/j.bbrc.2009.12.176. Epub 2010 Jan 7.

Abstract

The protein tyrosine phosphatase-1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) have been implicated in down-regulation of tyrosine kinase receptors, conferring anti-oncogenic functions to these PTPases. However, recent work has shown that PTP1B is positively implicated in oncogenic properties of breast cancer cells by regulating the ERK pathway. Here, we studied the function of PTP1B and TC-PTP in IGF-2-induced growth, survival and migration of MCF-7 breast cancer cells. Using siRNA, we showed that reduction in the expression of these PTPases decreased cell growth and ERK phosphorylation. Reduction in the expression of these PTPases did not impair IGF-2 effects on cell survival to acute treatment with 4-OH Tamoxifen. In contrast, IGF-2-induced MCF-7 cell migration was markedly impaired by reduction of PTP1B or TC-PTP expression, independently of the ERK pathway. This novel finding reinforces the potential role of these PTPases as therapeutic targets for treatment of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Humans
  • Insulin-Like Growth Factor II / metabolism*
  • Insulin-Like Growth Factor II / pharmacology
  • Neoplasm Metastasis
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / genetics

Substances

  • RNA, Small Interfering
  • Insulin-Like Growth Factor II
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2