Mutational Spectra of PTEN/MMAC1 Gene: a Tumor Suppressor With Lipid Phosphatase Activity
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TLDR
The mutational spectra of the PTEN/MMAC1 gene in tumors from various tissues, especially endometrium, brain, prostate, and ovary, are reviewed, suggesting that depending on the tissue type, the gene appears to be involved in the initiation or the progression of cancers.Abstract:
PTEN/MMAC1 (phosphatase, tensin homologue/mutated in multiple advanced cancers) is a tumor suppressor protein that has sequence homology with dual-specificity phosphatases, which are capable of dephosphorylating both tyrosine phosphate and serine/threonine phosphate residues on proteins. The in vivo function of PTEN/MMAC1 appears to be dephosphorylation of phosphotidylinositol 3,4, 5-triphosphate. The PTEN/MMAC1 gene is mutated in the germline of patients with rare autosomal dominant cancer syndromes and in subsets of specific cancers. Here we review the mutational spectra of the PTEN/MMAC1 gene in tumors from various tissues, especially endometrium, brain, prostate, and ovary, in which the gene is inactivated very frequently. Germline and somatic mutations in the PTEN/MMAC1 gene occur mostly in the protein coding region and involve the phosphatase domain and poly(A)(6) stretches. Compared with germline alterations found in the PTEN/MMAC1 gene, there is a substantially increased frequency of frameshift mutations in tumors. Glioblastomas and endometrial carcinomas appear to have distinct mutational spectra, probably reflecting differences in the underlying mechanisms of inactivation of the PTEN/MMAC1 gene in the two tissue types. Also, depending on the tissue type, the gene appears to be involved in the initiation or the progression of cancers. Further understanding of PTEN/MMAC1 gene mutations in different tumors and the physiologic consequences of these mutations is likely to open up new therapeutic opportunities for targeting this critical gene.read more
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References
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Journal ArticleDOI
PTEN, a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Jing Li,Clifford Yen,Danny Liaw,Katrina Podsypanina,Shikha Bose,Steven I. Wang,Janusz Puc,Christa Miliaresis,Linda Rodgers,Richard W. McCombie,Sandra H. Bigner,Beppino C. Giovanella,Michael Ittmann,B. Tycko,Hanina Hibshoosh,Michael Wigler,Ramon Parsons +16 more
TL;DR: The PTEN product has a protein tyrosine phosphatase domain and extensive homology to tensin, a protein that interacts with actin filaments at focal adhesions as discussed by the authors.
Journal ArticleDOI
The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate
Tomohiko Maehama,Jack E. Dixon +1 more
TL;DR: It is demonstrated that overexpression of PTEN, a putative tumor suppressor, reduced insulin-induced PtdIns(3,4,5)P3 production in human 293 cells without effecting insulin- induced phosphoinositide 3-kinase activation.
Journal ArticleDOI
Identification of a candidate tumour suppressor gene, MMAC1 , at chromosome 10q23.3 that is mutated in multiple advanced cancers
Peter A. Steck,Mark A. Pershouse,Samar A. Jasser,W. K. A. Yung,Huai Lin,Azra H. Ligon,Lauren A. Langford,Michelle Baumgard,T. Hattier,Thaylon Davis,Cheryl Frye,Rong Hu,Bradley D. Swedlund,David H. F. Teng,Sean V. Tavtigian +14 more
TL;DR: The results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.
Journal ArticleDOI
Negative Regulation of PKB/Akt-Dependent Cell Survival by the Tumor Suppressor PTEN
Vuk Stambolic,Vuk Stambolic,Akira Suzuki,Akira Suzuki,José Luis de la Pompa,José Luis de la Pompa,Christine Mirtsos,Christine Mirtsos,Takehiko Sasaki,Takehiko Sasaki,Jürgen Ruland,Jürgen Ruland,Josef M. Penninger,Josef M. Penninger,David P. Siderovski,David P. Siderovski,Tak W. Mak,Tak W. Mak +17 more
TL;DR: The results show that PTEN may exert its role as a tumor suppressor by negatively regulating the PI3'K/PKB/Akt signaling pathway.
Journal ArticleDOI
New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
TL;DR: A series of publications over the past year now suggest a mechanism by which PTEN loss of function results in tumors, and PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position ofosphoinositides.
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