Overexpression of a synthetic phosphotyrosine protein phosphatase gene increases radiosensitivity in vitro of normal and transformed murine NIH/3T3 fibroblasts
✍ Scribed by Maria Alessandra Santucci; Joel S. Greenberger; Jacalyn H. Pierce; Lucio Babini; Enza Barbieri; Stefania Pacini; Stefania Rigacci; Claudia Pazzagli; Andrea Berti; Giovanni Raugei; Marco Ruggiero
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 712 KB
- Volume
- 4
- Category
- Article
- ISSN
- 1065-7541
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✦ Synopsis
Protein tyrosine phosphatases (PTPases) represent a family of enzymes which together with protein tyrosine kinases (PTKases) play a critical role in cell proliferation and are likely involved in neoplastic transformation. Results presented here indicate that PTPases may also be involved in mechanisms regulating radiation-induced cell damage and repair. Our conclusion arises from the influence of a completely unique PTPase, termed low Mr phosphotyrosine protein phosphatase, on cell radioresponse in vitro, relative to dose rate. Overexpression of this particular PTPase was induced in two clonal cell populations (murine fibroblast NIW3T3 and murine hematopoietic progenitor 32D cell lines) by transfection of a synthetic gene whose product shared functional identity with the native form of the enzyme. Moreover, our results provide evidence that the low Mr PTPase effect on radioresponse is intrinsically due to its overexpression and is not related to its ability to reverse malignant transformation. In fact, it was exploited on both the parental NIW3T3 cell line and subclones where cell transformation was induced by v-erbB, through constitutive phosphorylation of the epidermal growth factor (EGF) receptor (the substrate specifically dephosphorylated by this enzyme). The discrepancy between radiobiological activity of low Mr PTPase on the NIW3T3 and 32D cells lets us assume a cell-type-regulated PTPase specificity for the control of radiation-induced cell damage and repair, independent from PTPase interaction with specific signal transduction substrates. Clinical relevance for our study and use of endogenous levels of PTPase as a predictor of cell radioresponse must be substantiated by further studies, supporting the radiobiological effects of other classes of PTPase, specific counterregulators of the mitogenic signal of other cell types.