Histochemically demonstrable protein tyrosine phosphatase in human breast and colorectal cancer: large decrease in its activity in colorectal cancer suggests a tumor suppressor role in colorectal mucosal cells.
Many oncogene products and growth factor receptors are protein tyrosine kinases, and exert their cellular effects by the phosphorylation of tyrosyl residues of effector proteins. The balance and dynamic renewal of phosphotyrosine proteins are also regulated by protein tyrosine phosphatases (PTPs), whose inhibition under experimental conditions causes cellular proliferation and transformation, with a concomitant increase in phosphotyrosine protein content. Inverse effects are obtained by increasing PTP activity. On the basis of these effects, PTPs might also function as tumor suppressors in human tissues. This possibility was further investigated here by demonstrating PTP and phosphotyrosine protein content with histochemical techniques. In normal human breast tissue PTP activity was low and in the majority of breast cancers the activity was increased and exhibited great variation between different cases. When the relationship of phosphotyrosine protein content with PTP was evaluated, no inverse dependence was detected, suggesting that in human breast tissue and cancer PTP may not show tumor suppressor activity. In normal colorectal mucosae PTP activity was high, while in all colorectal cancers it was very low, constituting only 14% of the activity present in normal mucosal cells. The great drop in PTP activity together with reported alterations in a gene encoding a PTP and in a chromosome containing a PTP gene in colorectal cancer strongly suggest that PTP may function as a tumor suppressor in human colorectal mucosae. The decrease in PTP activity may be one factor stimulating or causing neoplastic proliferation in multistep colorectal carcinogenesis.
Partanen
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Department of Pathology, Jorvi Hospital, Espoo, Finland.
D000230:Adenocarcinoma / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology*; D015179:Colorectal Neoplasms / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D019000:Phosphotyrosine / Q000032:analysis; D017027:Protein Tyrosine Phosphatases / Q000032:analysis*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000032:analysis
D009363:Neoplasm Proteins; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D017027:Protein Tyrosine Phosphatases