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Titolo:
HIGH CANCER SUSCEPTIBILITY AND EMBRYONIC LETHALITY ASSOCIATED WITH MUTATION OF THE PTEN TUMOR-SUPPRESSOR GENE IN MICE
Autore:
SUZUKI A; DELAPOMPA JL; STAMBOLIC V; ELIA AJ; SASAKI T; BARRANTES ID; HO A; WAKEHAM A; ITIE A; KHOO W; FUKUMOTO M; MAK TW;
Indirizzi:
UNIV TORONTO,AMGEN INST,ONTARIO CANC INST TORONTO ON M5G 2C1 CANADA UNIV TORONTO,AMGEN INST,ONTARIO CANC INST TORONTO ON M5G 2C1 CANADA UNIV TORONTO,DEPT MED BIOPHYS & IMMUNOL TORONTO ON M5G 2C1 CANADA TOHOKU UNIV,INST DEV AGING & CANC,DEPT PATHOL SENDAI MIYAGI 9808575 JAPAN
Titolo Testata:
Current biology
fascicolo: 21, volume: 8, anno: 1998,
pagine: 1169 - 1178
SICI:
0960-9822(1998)8:21<1169:HCSAEL>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
GERMLINE MUTATIONS; COWDEN-DISEASE; MOUSE; PROTEIN; PTEN/MMAC1; BREAST; EXPRESSION; TISSUES; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
A. Suzuki et al., "HIGH CANCER SUSCEPTIBILITY AND EMBRYONIC LETHALITY ASSOCIATED WITH MUTATION OF THE PTEN TUMOR-SUPPRESSOR GENE IN MICE", Current biology, 8(21), 1998, pp. 1169-1178

Abstract

Background: Germ-line and sporadic mutations in the tumor suppressor gene PTEN (also known as MMAC or TEP1), which encodes a dual-specificity phosphatase, cause a variety of cancers such as Cowden disease, glioblastoma, endometrial carcinoma and prostatic cancer. PTEN is widely expressed, and Cowden disease consistently affects various organ systems, suggesting that the PTEN protein must have an important, although as yet poorly understood, function in cellular physiology. Results: Homozygous mutant mice lacking exons 3-5 of the PTEN gene (mPTEN(3-5)) had severely expanded and abnormally patterned cephalic and caudal regions at day 8.5 of gestation. Embryonic death occurred by day 9.5 and was associated with defective chorio-allantoic development. Heterozygous mPTEN3-5 mice had an increased incidence of tumors, especially T-cell lymphomas; gamma-irradiation reduced the time lapse of tumor formation. DNA analysis of these tumors revealed the deletion of the mPTEN gene due to loss of heterozygosity of the wild-type allele. Tumors associated with loss of heterozygosity in mPTEN showed elevated phosphorylation of protein kinase B (PKB, also known as Akt kinase), thus providing a functional connection between mPTEN and a murine proto-oncogene (c-Akt) involved in the development of lymphomas. Conclusions: The mPTEN gene is fundamental for embryonic development in mice, as mPTEN3-5 mutant embryos died by day 9.5 of gestation, with patterning defects incephalic and caudal regions and defective placentation. Heterozygous mice developed lymphomas associated with loss of heterozygosity of thewildtype mPTEN allele, and tumor appearance was accelerated by gamma-irradiation, These lymphomas had high levels of activated Akt/PKB, theprotein product of a murine proto-oncogene with anti-apoptotic function, associated with thymic lymphomas. This suggests that tumors associated with mPTEN loss of heterozygosity may arise as a consequence of an acquired survival advantage. We provide direct evidence of the role of mPTEN as a tumor suppressor gene in mice, and establish the mPTEN mutant mouse as an experimental model for investigating the role of PTEN in cancer progression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 03:44:00