Protein tyrosine phosphatases (PTPs) have long been thought to play a role in tumor suppression due to their ability to antagonize the growth promoting protein tyrosine kinases. Recently, a candidate tumor suppressor from 10q23, termed P-TEN, was isolated, and sequence ho- mology was demonstrated with members of the PTP family, as well as the cytoskeletal protein tensin. Here we show that recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity phospha- tase. In addition, P-TEN exhibited a high degree of substrate specificity, showing selectivity for extremely acidic substrates in vitro. Furthermore, we demonstrate that mutations in P-TEN, identified from primary tumors, tumor cells lines, and a patient with Bannayan-Zonana syndrome, resulted in the ablation of phosphatase activity, demonstrating that enzy- matic activity of P-TEN is necessary for its ability to function as a tumor suppressor.

http://www.pnas.org/content/94/17/9052.full.pdf

P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase (cancerytyrosine phosphorylationysignal transductionyprotein tyrosine phosphatase)

Abnormal distribution of hDlg and PTEN in premalignant lesions and invasive cervical cancer

Maxwell GL, Risinger JI, Shaw H, Alvarez A, Barrett JC, Futreal A, Berchuck A Mutations in the PTEN tumor suppressor gene in cervical carcinomas Int J Gynecol Cancer 1998; 8: 489–493



To elucidate further the molecular pathogenesis of cervical cancer we sought to determine whether mutations in the PTEN tumor suppressor gene are a feature of these cancers Genomic DNA was extracted from 67 primary cervical cancers and 9 immortalized cervical cancer cell lines Using the polymerase chain reaction, the nine exons and intronic splice sites of the PTEN gene were amplified using 11 primer pairs Single strand conformation polymorphism analysis was used to screen for mutations in the PTEN gene and variant bands were subjected to DNA sequencing The primary cancers were also tested for the presence of HPV DNA Mutations in the PTEN gene were not detected in any of the immortalized cell lines, but sequence alterations were noted in 4/67 (6%) primary cervical cancers Three mutations resulted in frameshifts that predict truncated protein products, including two cases in which we found an identical 4-base-pair deletion in codons 318–319 In addition, a one-base-pair insertion in codon 320 was seen in another case Finally, a missense mutation (G143 A) was observed immediately adjacent to the catalytic site of the phosphatase domain in exon 5 In two cases with PTEN mutations in which corresponding normal DNA was available, loss of the wild type allele was demonstrated There was no apparent relationship between the presence of a PTEN mutation and pathologic features or the presence of human papillomavirus DNA Although mutations in the PTEN gene are found in only a small fraction of cervical cancers, alterations of this tumor suppressor gene may play a role in the development of some of these cancers

Barrett

Papers

Mutations in the PTEN tumor suppressor gene in cervical carcinomas