title: Putative role of the mTOR/4E-BP1 signaling pathway in the carcinogenesis and progression of gastric cardiac adenocarcinoma.
abstract: The mammalian target of rapamycin/eukaryotic translation inititiation factor 4E binding protein 1 (mTOR/4E-BP1) transduction pathway is activated in a range of malignant cancers, but its role in human gastric cardiac adenocarcinoma (GCA) has not been well defined. The present study used western blotting and reverse transcription polymerase chain reaction (RT-PCR) to assess the expression of mTOR, 4E-BP1 and eukaryotic translation initiation factor 4E (eIF4E) at the protein and mRNA levels in 33 cases of GCA and paired adjacent normal gastric mucosal tissues. The expression of mTOR at the protein level in GCA was significantly lower than that in the corresponding normal gastric mucosa (0.296 ± 0.27 vs. 1.348 ± 0.80, P<0.05), but the ratio of p-mTOR to mTOR was significantly increased in tumor tissues (1.425 ± 1.07 vs. 0.450 ± 0.24, P<0.05). The expression of 4E-BP1 was significantly decreased in GCA compared with normal tissues (p<0.05), while the levels of phosphorylated 4E-BP1 (p-4E-BP1) were markedly increased in tumor tissues (p<0.05). The levels of phosphorylated eIF4E (p‑eIF4E) were significantly higher in the tumors in comparison to the corresponding normal tissues (1.822 ± 0.63 vs. 0.997 ± 0.38, P<0.05), and the levels of p-eIF4E were closely correlated with lymph node metastasis (p<0.05). The mTOR/4E-BP1 signaling pathway is activated in GCA, with mTOR activated mainly through increased mTOR phosphorylation rather than protein overexpression.
authors.affiliation: Department of Pathology, The Second Hospital, Hebei Medical University,                     Shijiazhuang 050000, P.R. China.
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Yang
authors.forename: Li Ying
authors.initials: LY
authors.lastname: Xue
authors.forename: Ling Xiao
authors.initials: LX
authors.lastname: Xing
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Jun Ling
authors.initials: JL
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Yan
authors.forename: Xiang Hong
authors.initials: XH
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D018797:Cell Cycle Proteins; D018450:Disease Progression; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D039561:Eukaryotic Initiation Factor-4E; D010750:Phosphoproteins; D012333:RNA, Messenger; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases