title: Expression of eukaryotic initiation factor 4E and 4E binding protein 1 in colorectal carcinogenesis.
abstract: Cap dependent translation is mainly regulated at the level of the eukaryotic initiation factor 4E (eIF4E), the activity of which is controlled by phosphorylation and sequestration by its well established regulator, 4E binding protein 1 (4E-BP1). Both eIF4E and 4E-BP1 have been shown to be involved in the malignant progression of multiple human cancers, including colorectal cancer. However, the data on determining the expression of eIF4E, 4E-BP1 and their phosphorylated forms simultaneously in a single patient with colorectal cancer is lacking. Therefore the aim of our study was to explore the roles of these factors in colorectal carcinogenesis by immunohistostaining colorectal tissues (normal, low grade adenoma, high grade adenoma, and adenocarcinoma). Our results showed that the expression levels of eIF4E increased steadily as the cancer progressed from the case of benign dysplasia to an adenocarcinoma; all the while maintaining an unphosphorylated form. On the other hand, total expression levels of 4E-BP1 increased only in the premalignant state of the disease and decreased (but highly phosphorylated or inactivated) or abolished upon malignancy. Taken together, our findings suggest that strong correlations exist between the expression of eIF4E (not p-eIF4E) and tumor grade providing evidence that eIF4E expression plays a pivotal role in the malignant progression of colorectal cancer. Moreover, 4E-BP1 showed a bi-phasic level of expression during carcinogenesis, which is expressed only in hyperplasic or dysplastic tissues as an endogenous tumor suppressor molecule.
authors.affiliation: Molecular Tumorigenesis and Anticancer Pharmacology, EDST, Lebanese University Hadath, Lebanon.
authors.forename: Mona
authors.initials: M
authors.lastname: Diab-Assaf
authors.affiliation: Molecular Tumorigenesis and Anticancer Pharmacology, EDST, Lebanese University Hadath, Lebanon.
authors.forename: Raefa
authors.initials: R
authors.lastname: Abou-Khouzam
authors.affiliation: Molecular Tumorigenesis and Anticancer Pharmacology, EDST, Lebanese University Hadath, Lebanon.
authors.forename: Nina
authors.initials: N
authors.lastname: Saadallah-Zeidan
authors.affiliation: Specialized Medical Laboratory Al-Mazraa, Beirut, Lebanon.
authors.forename: Khaled
authors.initials: K
authors.lastname: Habib
authors.affiliation: Faculty of Medicine, Lebanese University Hadath, Lebanon.
authors.forename: Nizar
authors.initials: N
authors.lastname: Bitar
authors.affiliation: Molecular Tumorigenesis and Anticancer Pharmacology, EDST, Lebanese University Hadath, Lebanon.
authors.forename: Walid
authors.initials: W
authors.lastname: Karam
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, University of Limoges FR 3503 GEIST, EA1069, GDR CNRS 3049, Limoges, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Liagre
authors.affiliation: Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University Kingdom of Saudi Arabia.
authors.forename: Steve
authors.initials: S
authors.lastname: Harakeh
authors.affiliation: Molecular Tumorigenesis and Anticancer Pharmacology, EDST, Lebanese University Hadath, Lebanon.
authors.forename: Rania
authors.initials: R
authors.lastname: Azar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D006801:Humans; D060787:Neoplasm Grading; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins
keywords: 4E-BP1; Colorectal cancer; eIF4E; immunuhistochemistry; translational control