Tyrosine phosphate in melanoma progression.
BACKGROUND
Cellular tyrosine phosphorylation is regulated by two large families of enzymes. Protein tyrosine kinases (PTK) mediate addition, and protein tyrosine phosphatases (PTP), removal of phosphate from protein substrates. PTKs are oncogenes and PTPs have been hypothesized to function as tumour suppressor genes.


OBJECTIVE
To determine changes in tyrosine phosphate and PTP activity that occur during melanoma progression.


METHODS
Immunohistochemistry was used to study phosphotyrosine in melanocytic lesions. In addition, PTP activity of normal melanocytes and melanoma cell lines was measured using an enzyme-linked immunosorbent assay-based system.


RESULTS
Melanocytes in normal skin and most (67%) benign naevi were not immunostained. Neither were early malignant lesions (80% of malignant melanoma in situ and radial growth phase melanomas) stained. However, most advanced melanomas (100% of vertical growth phase, and 90% of metastatic melanomas) were immunoreactive. When total PTP enzyme activity was assayed in normal melanocytes and malignant melanoma cell lines, there was a significant increase in activity associated with melanoma progression.


CONCLUSIONS
Taken together, the data suggest increased phosphotyrosine signalling occurs during melanoma progression at the stage when cells first become competent for metastasis.
McArdle
L
L
Department of Pathology, Conway Institute, University College Dublin, Dublin 4, Ireland.
Bergin
O
O
Fallowfield
M E
ME
Dervan
P A
PA
Easty
D J
DJ
D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D008544:Melanocytes / Q000201:enzymology; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism* / Q000556:secondary; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019000:Phosphotyrosine; D017027:Protein Tyrosine Phosphatases