title: Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues.
abstract: Eukaryotic translation initiation factor 4E (eIF4E) is a rate-limiting factor for cap-dependent protein synthesis and is regulated by PI3 kinase/mTOR and mitogen-activated protein kinase (MAPK)/Mnk signaling pathways. Recent studies have shown that Mnk-mediated eIF4E phosphorylation is absolutely required for eIF4E's oncogenic function. Overexpression of eIF4E has been reported in many types of cancers; however, the expression of phosphorylated eIF4E (p-eIF4E) in human cancer tissues, particularly solid tumor tissues, has not been reported. The current study focused on evaluating p-eIF4E expression patterns in the tumor tissues obtained from patients with a variety of malignancies. Using three different tissue microarrays consisting of a total of 380 cases of human cancers and 146 cases of adjacent normal tissues, we detected p-eIF4E positive staining in 63.4% (241/380) of cancers, but only in 30.1% (44/146) of adjacent normal tissues. Thus, p-eIF4E expression is significantly higher in cancers than in adjacent normal tissues (p < 0.001). In general, there was no major difference in p-eIF4E staining between cancers with and without lymph node metastasis. In certain types of maligancies such as lung, gastric and colorectal cancers, p-eIF4E staining was significantly higher in the early stage (T1) than in the late stage (T3) disease (p < 0.05). Collectively, these findings suggest that p-eIF4E may play a critical role in cancer development, particularly early stages of tumorigenesis and support p-eIF4E as a good cancer therapeutic target.
authors.affiliation: Department of Hematology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Songqing
authors.initials: S
authors.lastname: Fan
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
authors.forename: John
authors.initials: J
authors.lastname: Kauh
authors.forename: Zhiheng
authors.initials: Z
authors.lastname: Xu
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Sun
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000473:pathology; D039561:Eukaryotic Initiation Factor-4E / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008175:Lung Neoplasms / Q000737:chemistry / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis* / Q000378:metabolism; D009369:Neoplasms / Q000737:chemistry* / Q000473:pathology; D009928:Organ Specificity; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000378:metabolism; D040081:Protein Array Analysis; D011499:Protein Processing, Post-Translational
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D009363:Neoplasm Proteins