PURPOSE: PTEN/MMAC1/TEP1 is a tumor suppressor gene encoding a dual-specificity protein phosphatase with homology to the cytoskeleton proteins, chicken tensin and bovine auxilin. PTEN mutations have been described in several types of human cancer. Recently, mutations at an (A)(6) repeat of PTEN exons 7 and 8 in colorectal cancer (CRC) patients with microsatellite instability have been detected. Moreover, an involvement of the transforming growth factor (TGF)-beta pathway in hereditary colorectal syndromes has been proposed. EXPERIMENTAL DESIGN: In this study, we analyzed the frequency of PTEN gene mutations in 36 CRC patients and 5 colon cancer cell lines. Furthermore, in 16 of 36 patients, microsatellite instability and TGF-beta receptor II analysis was possible. The study was performed by PCR and automated sequencing of the entire coding region of the PTEN gene. RESULTS: About 17% of colon cancer patients and one of five (HSR 320) colon cancer cell lines had mutations. Mutations were detected only among patients with locally advanced or metastatic CRC. PTEN mutations were detected in three of five (60%) patients showing both microsatellite instability and TGF-beta receptor II mutations. These patients presented with advanced or metastatic CRC CONCLUSIONS: Overall, these results show that PTEN alteration together with TGF-beta pathway inactivation could contribute to tumorigenesis and metastatic spread of sporadic and microsatellite unstable CRC.
PURPOSE:PTEN/MMAC1/TEP1 is a tumor suppressor gene encoding a dual-specificity protein phosphatase with homology to the cytoskeleton proteins, chickentensin and bovineauxilin. PTEN mutations have been described in several types of humancancer. Recently, mutations at an (A)(6) repeat of PTEN exons 7 and 8 in colorectal cancer (CRC) patients with microsatellite instability have been detected. Moreover, an involvement of the transforming growth factor (TGF)-beta pathway in hereditary colorectal syndromes has been proposed. EXPERIMENTAL DESIGN: In this study, we analyzed the frequency of PTEN gene mutations in 36 CRC patients and 5 colon cancer cell lines. Furthermore, in 16 of 36 patients, microsatellite instability and TGF-beta receptor II analysis was possible. The study was performed by PCR and automated sequencing of the entire coding region of the PTEN gene. RESULTS: About 17% of colon cancerpatients and one of five (HSR 320) colon cancer cell lines had mutations. Mutations were detected only among patients with locally advanced or metastatic CRC. PTEN mutations were detected in three of five (60%) patients showing both microsatellite instability and TGF-beta receptor II mutations. These patients presented with advanced or metastatic CRC CONCLUSIONS: Overall, these results show that PTEN alteration together with TGF-beta pathway inactivation could contribute to tumorigenesis and metastatic spread of sporadic and microsatellite unstable CRC.
Authors: Rosalia Rabinovsky; Panisa Pochanard; Chontelle McNear; Saskia M Brachmann; Jonathan S Duke-Cohan; Levi A Garraway; William R Sellers Journal: Mol Cell Biol Date: 2009-07-27 Impact factor: 4.272
Authors: Stayce E Beck; Barbara H Jung; Antonio Fiorino; Jessica Gomez; Eunice Del Rosario; Betty L Cabrera; Sherry C Huang; Jimmy Y C Chow; John M Carethers Journal: Am J Physiol Gastrointest Liver Physiol Date: 2006-07 Impact factor: 4.052
Authors: Marianne Berg; Stine A Danielsen; Terje Ahlquist; Marianne A Merok; Trude H Ågesen; Morten H Vatn; Tom Mala; Ole H Sjo; Arne Bakka; Ingvild Moberg; Torunn Fetveit; Øystein Mathisen; Anders Husby; Oddvar Sandvik; Arild Nesbakken; Espen Thiis-Evensen; Ragnhild A Lothe Journal: PLoS One Date: 2010-11-12 Impact factor: 3.240
Authors: Adam Naguib; James C Cooke; Lisa Happerfield; Lucy Kerr; Laura J Gay; Robert N Luben; Richard Y Ball; Panagiota N Mitrou; Alison McTaggart; Mark J Arends Journal: BMC Cancer Date: 2011-04-07 Impact factor: 4.430