Low molecular weight protein tyrosine phosphatase genetic polymorphism and susceptibility to cancer development.
Low molecular weight protein tyrosine phosphatases (LMW-PTPs) are a family of 18-kDa enzymes involved in cell growth regulation. Human acid phosphatase 1 (ACP1) is genetically polymorphic, and three common alleles segregating at the ACP1 locus on the short arm of chromosome 2 give rise to six phenotypes. Each allele appears to encode two electrophoretically different isozymes, fast and slow, which are produced in allele-specific ratios. Fast isozymes are related with cytoskeletal organization, cellular organization, and spreading. Slow isozymes are associated with growth factor receptors and dephosphorylation. In this study, ACP1 genetic polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism on 74 subjects with various cancers; the control group was 236 healthy subjects randomly selected. With genotypes cumulated according to fast isoform concentration, [A + AC] < [AB + BC] < [BB], subjects with cancer presented an increase of fast isozyme concentration (BB 38.2%; P = 0.002, chi2), relative to the control sample (19.8%). The increase of fast isozyme concentration increased the invasive capacity of cancer cells, whereas a decrease of slow isozyme concentration in cancer did not cause growth inhibition and so resulted in cancer cell proliferation.
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Genetics Laboratory, Metabolism and Endocrinology Center, Lisbon Medical School, Av. Prof. Egas Moniz, Edifício Egas Moniz, P1C, 1649-028 Lisbon, Portugal. irinabq@portugalmail.pt
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D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008970:Molecular Weight; D009369:Neoplasms / Q000145:classification / Q000201:enzymology* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D017931:DNA Primers; D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases