title: Immunohistochemical analysis of phosphorylated mammalian target of rapamycin and its downstream signaling components in invasive breast cancer.
abstract: The present study aimed to investigate whether the mammalian target of rapamycin (mTOR) signaling pathway is activated in invasive breast cancer. The expression levels of phosphorylated (p)‑mTOR at ser2448 were detected, as well as the expression levels of its downstream signaling molecules: Eukaryotic translation initiation factor 4E‑binding protein 1 (4E‑BP1), and p70 ribosomal protein S6 kinase 1 (S6K1). The correlation between p‑mTOR, p‑4E‑BP1, p‑S6K1, and the clinicopathological parameters of breast cancer were also determined. p‑mTOR, p‑4E‑BP1 and p‑S6K1 expression was detected in 285 breast cancer tumor samples and adjacent normal tissue samples using immunohistochemistry. The expression levels and the location of the proteins were analyzed and compared in the various tissue samples. Multivariate Cox regression was used to analyze the clinicopathological factors and prognosis associated with the tissue samples. The disease‑free survival rate was examined using survival analyses and Log‑rank tests. The results of the present study indicated that the expression levels of p‑mTOR, p‑4E‑BP1, and p‑S6K1 were significantly higher in breast cancer tissue, as compared with normal tissue (P<0.01). p‑mTOR was predominantly expressed in the cytoplasm, whereas p‑4E‑BP1 and p‑S6K1 were predominantly co‑expressed in the cytoplasm and the nucleus. In addition, p‑4E‑BP1 and p‑S6K1 were more likely to be expressed in the cytoplasm in breast cancer tissue samples, as compared with normal tissue samples (P<0.001). Positive p‑mTOR was not significantly correlated with positive p‑4E‑BP1 and p‑S6K1 expression. The survival analyses of the patients with positive p‑mTOR, p‑4E‑BP1, and p‑S6K1 tissue samples were not significantly different from those of the patients with negative tissue samples (P>0.05). Thus suggesting that these markers are not adequate risk factors for disease free survival (P>0.05). In conclusion, the results of the present study suggested that p‑mTOR, p‑4E‑BP1, and p‑S6K1 are activated in invasive breast cancer. In addition, the exclusive expression of p‑4E‑BP1 and p‑S6K1 in the cytoplasm may be characteristic of progressive breast cancer. However, p‑mTOR, p‑4E‑BP1, and p‑S6K1 are not prognostic factors for breast cancer.
authors.affiliation: Department of Breast and Neck, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
authors.forename: Bin-Lin
authors.initials: BL
authors.lastname: Ma
authors.affiliation: Department of Breast and Neck, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
authors.forename: Mei-Hui
authors.initials: MH
authors.lastname: Shan
authors.affiliation: Department of Breast and Neck, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Breast and Neck, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Ren
authors.affiliation: Department of Breast and Neck, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Epidemiology and Health Statistics, Public Health College of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Pathology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D018797:Cell Cycle Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1