| pubmed-article:20838824 | pubmed:abstractText | Aberrant activation of phosphoinositide-3 kinase/Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) signaling is implicated in the pathogenesis of mantle cell lymphoma (MCL). We previously showed oncogenic activation of PI3K/Akt pathway in a subset of MCL patients. In this study, we investigated downstream the immunohistochemical expression of (Ser2448)pmTOR [indicative of mTOR complex 1 (mTORC1) activation status] as well as of hypoxia-inducible factor 1 alpha (HIF-1?), hypoxia-inducible factor 2 alpha (HIF-2?), p53, and p21 in the same series of MCL patients. Additionally, correlation of these proteins with activated Akt ((Ser473)pAkt) and established histological prognostic factors was examined. Thirty-five tissue samples (28 classical type and seven blastoid variant) were included. The neoplastic cells expressed (Ser2448)pmTOR in 61.7%, HIF-1? in 73.5%, HIF-2? in 23.5%, and p53 in 18.2% of patients, while p21 was negative in all examined samples. In addition, 72% of patients who expressed HIF-1? had also (Ser2448)pmTOR expression (p?=?0.041). HIF-1? expression was also correlated to an elevated (?30%) Ki-67 (p?=?0.031) and blastoid variant of disease (p?=?0.017). In conclusion, we report for the first time common expression of HIF-alphas, especially HIF-1?, in MCL patients. Furthermore, an overall activation of mTORC1?HIF-1? axis and a potential role of (Ser2448)pmTOR in the regulation of HIF-1? in MCL patients are suggested. Finally, HIF-1? appears to be associated with more aggressive disease. A pathogenetic role for both mTORC1 and HIF-1? in MCL is implied, which will possibly lead to more efficient target therapies. | lld:pubmed |
