Overexpression of the Protien Tyrosine Phosphatase PTP1B in Human Breast Cancer: Assocation With p185c-erbB-2 Protein Expression

Abstract

The p185 ^c-erbB-2 growth factor receptor protien tyrosine kinase (PTK) is overexpressed in one third of human breast cancer patients and indicates a poor prognosis in these patients. Protien tyrosine phosphatases (PTPs) may balance PTK activity as part of normal growth-regulation pathways. PTP1B is an intracelluar PTP that is involved in linkage between signal transduction pathways and may interface with inappropriate PTK activity in transformed cells. The aim of this study was to determine if PTP1B is overexpression in human mammary tumors and to determine if such overexpression is associated with the overexpression of the p185 ^c-erbB-2 receptor PTK. Our samples were frozen sections from 29 human mammary tumors (19 pure infiltrating, two pure intraductal, and eight combined intraductal and infiltrating) and nine sections from normal breast tissue. The sections were immunohisto-chemically stained for PTP1B and p185 ^c-erb-2 , and the results were analyzed statistically for association between overexpression of the two proteins. Northern blot analysis was used to assess if PTP1B overexpression was coincident with increased transcription of the PTP1B gene. Overxpression of the PTP1B protein was observed in 72.4% of the tumor sections compared with normal epithelium, with maximal expression occurring in 37.9% of the tumors. All of the tumor subtypes, including the pure intradutal lesions, overexpressed PTP1B. Statistical analyses demonstrated a significant association between PTP1B overexpression and breast cancer ( P <.038) and between the overexpression of PTP1B and the overexpression of PTP1D and the overexpression of p185 ^e-erbB-2 ( P <.006). PTP1B messenger RNA steady-state transcription was consistently increased in tumors versus normal tissues. PTP1B overexpression is a common phenotypic manifestation in human breast cancers and is associated with overexpression of p185 ^e-erbB-2 . Steadystate PTP1B transcription is in creased in tumor tissue. Further studies are needed to determine if PTP1B overexpression balances or augments PTK activity. PTP1B overexpression might also be evaluated as a clinical prognostic factor in human breast cancers. [J Natl Cancer Inst 86:372−378, 1994]