Brady, Garrett, Crean, St John, Lorenzon, Ana and Kapas, Supriya (2008) IGF-I protects human oral buccal mucosal epithelial cells from sodium nitroprusside-induced apoptosis via PI3-kinase. Growth Hormone & IGF Research, 18 (4). pp. 298-306. ISSN 10966374
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Official URL: http://dx.doi.org/10.1016/j.ghir.2007.11.006
Cancers of the head and neck account for the vast majority of all malignancies of the oral cavity. The insulin-like growth factor (IGF) family of proteins is well documented to have an important role in rescuing cells from apoptosis. While it is known the IGF proteins are present in normal oral epithelial and cancer cells its role is not fully understood. Our aim was to study the ability of IGFs to rescue sodium nitroprusside (SNP)-induced apoptotic normal oral epithelial cells in vitro.
Cultured normal human oral keratinocytes (NOKs) or epithelial cells were used. Apoptosis was induced by SNP then cells were exposed to IGF-I or IGF-II to rescue them. Cell viability was assessed by ELISA (for cell death and caspase 3) and FACS analysis; post receptor effects of IGF-I or IGF-II were assessed by [3H] thymidine incorporation. Cell signaling events were measured by western blotting using antibodies against phosphorylated Akt or p42/p44 MAPK, and measuring PI3-K activity by ELISA.
SNP induced apoptosis of NOKs and activated the PI3-K/Akt survival pathway. Exposing cells to IGF proteins prevented their apoptosis. IGF-I and -II caused significant increases in PI3-K, but not MAPK, activity. SNP and LY294002, a PI3-K inhibitor, both caused a significant rise in caspase 3 release from NOKs which was reduced in the presence of IGFs.
The data establishes the importance of IGF-activated PI3-K in rescuing cells from apoptosis. It lends further evidence to the significance of IGF proteins in the possible development of oral cancer.
|Uncontrolled Keywords (separate with ;):||Apoptosis; Cancers of the head and neck; Insulin-like growth factor; PI3-k/Akt signaling pathway; Oral keratinocytes; Squamous cell carcinoma|
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)|
R Medicine > RK Dentistry
|Schools:||College of Health and Wellbeing > School of Health|
|Deposited By:||Mehmood Kadir Mulla|
|Deposited On:||08 Mar 2012 16:02|
|Last Modified:||25 Jun 2012 10:04|
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