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Effect of protein tyrosine phosphatase 1B expression on transformation by the human neu oncogene
S Brown-Shimer1, K A Johnson, D E Hill
1Applied bioTechnology, Division of Oncogene Science, Cambridge, Massachusetts 02142.
Abstract:
Many oncogenes encode proteins with a tyrosine kinase activity that appears to be directly involved in the process of transformation. Because these kinases are themselves activated for transformation by tyrosine phosphorylation, proteins which remove phosphate from tyrosine residues, protein tyrosine phosphatases (also termed phosphotyrosine phosphatases and protein phosphotyrosyl phosphatases), are intuitive candidate transformation suppressors. The human PTP1B gene, previously cloned in our laboratory and encoding the low molecular weight protein tyrosine phosphatase PTPase 1B, was introduced into NIH 3T3 cells. Subsequent transformation of these PTPase 1B-expressing cells by an oncogenic form of the human neu gene was suppressed relative to control NIH 3T3 cells. This suppression of transformation was observed in assays for focus formation, anchorage-independent growth, and tumorigenicity. Tumorigenicity assays indicated a complex effect of PTPase 1B expression on transformation.
Insights
Introducing the human PTP1B gene into NIH 3T3 cells suppressed oncogene-induced cell transformation. This protein tyrosine phosphatase (PTPase 1B) inhibited focus formation, anchorage-independent growth, and tumorigenicity.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Many oncogenes encode tyrosine kinases crucial for cell transformation.
- Tyrosine phosphorylation activates these kinases, making protein tyrosine phosphatases (PTPases) potential tumor suppressors.
Purpose of the Study:
- To investigate the role of human PTP1B as a transformation suppressor.
- To determine if PTPase 1B expression can inhibit oncogene-induced cell transformation.
Main Methods:
- The human PTP1B gene was introduced into NIH 3T3 cells.
- These modified cells were then transformed using an oncogenic neu gene.
- Transformation was assessed via focus formation, anchorage-independent growth, and tumorigenicity assays.
Main Results:
- PTPase 1B expression significantly suppressed focus formation and anchorage-independent growth.
- Tumorigenicity assays revealed a complex inhibitory effect of PTPase 1B on transformation.
- NIH 3T3 cells expressing PTP1B showed reduced transformation compared to control cells.
Conclusions:
- PTP1B acts as a suppressor of oncogene-induced cell transformation.
- PTPase 1B demonstrates potential as a therapeutic target in cancer treatment.
- The findings highlight the critical role of protein tyrosine phosphatases in regulating cell transformation.