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Titolo:
Inhibition of mammary epithelial apoptosis and sustained phosphorylation of Akt/PKB in MMTV-IGF-II transgenic mice
Autore:
Moorehead, RA; Fata, JE; Johnson, MB; Khokha, R;
Indirizzi:
Univ Toronto, Dept Med Biophys, Ontario Canc Inst, Univ Hlth Network, Toronto, ON M5G 2M9, Canada Univ Toronto Toronto ON Canada M5G 2M9 twork, Toronto, ON M5G 2M9, Canada Univ Toronto, Dept Lab Med & Pathobiol, Ontario Canc Inst, Univ Hlth Network, Toronto, ON M5G 2M9, Canada Univ Toronto Toronto ON Canada M5G 2M9 twork, Toronto, ON M5G 2M9, Canada
Titolo Testata:
CELL DEATH AND DIFFERENTIATION
fascicolo: 1, volume: 8, anno: 2001,
pagine: 16 - 29
SICI:
1350-9047(200101)8:1<16:IOMEAA>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-I; PROGRAMMED CELL-DEATH; MESSENGER-RIBONUCLEIC-ACID; FACTOR BINDING-PROTEINS; HUMAN-BREAST-CANCER; GLAND INVOLUTION; GENE-EXPRESSION; INDUCED TUMORIGENESIS; BAD PHOSPHORYLATION; SIGNALING PATHWAYS;
Keywords:
IGF-II; transgenic mice; mammary involution; apoptosis; Akt/PKB;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
87
Recensione:
Indirizzi per estratti:
Indirizzo: Khokha, R Univ Toronto, Dept Med Biophys, Ontario Canc Inst, Univ Hlth Network, 610 Univ Ave, Toronto, ON M5G 2M9, Canada Univ Toronto 610 Univ Ave Toronto ON Canada M5G 2M9 2M9, Canada
Citazione:
R.A. Moorehead et al., "Inhibition of mammary epithelial apoptosis and sustained phosphorylation of Akt/PKB in MMTV-IGF-II transgenic mice", CELL DEAT D, 8(1), 2001, pp. 16-29

Abstract

IGF-II is a growth factor implicated in human cancers and animal tumor models. While the mitogenic properties of IGF-II are well documented, its ability to suppress apoptosis in vivo has never been proven, We generated independent MMTV-IGF-II transgenic mice to examine the control of epithelial apoptosis at the morphological, cellular and molecular levels during the physiological event of postlactation mammary involution. Transgenic IGF-11 expression was achieved in mammary epithelium and increased IGF-II bioactivity was confirmed by phosphorylation of the insulin receptor substrate-1, a signaling molecule downstream of the type I IGF receptor. IGF-II overexpressioninduced a delay in mammary involution, as evident by increased mammary gland to body weight ratios and persistence of both functionally intact lobuto-alveoli and mammary epithelial cellularity. The delayed mammary involutionresulted from a significant reduction in mammary epithelial apoptosis, andnot from increased epithelial proliferation. Recombinant IGF-II pellets implanted into involuting mammary glands of wild-type mice provided further evidence that IGF-II protein inhibited local epithelial apoptosis, At the molecular level, phosphorylated Akt/PKB, but not Erk1 or Erk2, persisted in IGF-II overexpressors and temporally correlated with reduced epithelial apoptosis. Levels of the phosphatase PTEN were unaltered in the transgenic tissue suggesting that the maintenance of Akt/PKB phosphorylation resulted fromsustained phosphorylation rather than altered dephosphorylation of PIP-3, Together, this data reveal that IGF-II inhibits apoptosis in vivo and this effect correlates with prolonged phosphorylation of Akt/PKB.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 13:00:06