| First Author | Moorehead RA | Year | 2001 |
| Journal | Cell Death Differ | Volume | 8 |
| Issue | 1 | Pages | 16-29 |
| PubMed ID | 11313699 | Mgi Jnum | J:95899 |
| Mgi Id | MGI:3527952 | Doi | 10.1038/sj.cdd.4400762 |
| Citation | Moorehead RA, et al. (2001) Inhibition of mammary epithelial apoptosis and sustained phosphorylation of Akt/PKB in MMTV-IGF-II transgenic mice. Cell Death Differ 8(1):16-29 |
| abstractText | 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-II 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 overexpression induced a delay in mammary involution, as evident by increased mammary gland to body weight ratios and persistence of both functionally intact lobulo-alveoli and mammary epithelial cellularity. The delayed mammary involution resulted from a significant reduction in mammary epithelial apoptosis, and not 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 from sustained 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 |
