Evaluation of the Immunohistochemical Staining Pattern of the mTOR Signaling Proteins in Colorectal Cancers and Adenoma Lesions
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Changes in the mammalian target of the rapamycin (mTOR) signaling proteins have been observed in many types of cancer. Accordingly, these proteins have recently become an exciting new target for molecular therapeutics. This study examined the expression of an activated mTOR signaling protein in patients with colorectal adenocarcinoma (CRAC) and colorectal adenoma lesion. Immunohistochemical analysis was performed on human CRAC and adenoma for the mTOR signaling components, including mTOR, phosphorylation, and activation of S6 kinase (p70-S6K), S6 ribosomal protein (S6), and eukaryotic initiation factor 4E-binding protein (4EBP1). A total of 100 cases with colorectal adenocarcinoma (CARC; N=40), adenoma with high-grade intraepithelial neoplasms (HIN; N=30), and adenoma with low-grade intraepithelial neoplasms (LIN; N=30) were enrolled in this study. p-mTOR expression was observed in 30 cases of the CRAC tissues (75%), 9 cases of adenoma with HIN (30%), and 2 cases of adenoma with LIN (7%). In addition, p-S6 expression was observed in 22 cases of CRAC tissues (55%), 8 cases of adenoma with HIN (27%), and 3 cases of adenoma with LIN (10%). A significant correlation was observed among the p-mTOR, p-S6 expression, and the adenoma–carcinoma sequence. Interestingly, the p-S6 protein was activated more in early CRAC than in advanced CRAC.
Abstract
Changes in the mammalian target of the rapamycin (mTOR) signaling proteins have been observed in many types of cancer. Accordingly, these proteins have recently become an exciting new target for molecular therapeutics. This study examined the expression of an activated mTOR signaling protein in patients with colorectal adenocarcinoma (CRAC) and colorectal adenoma lesion. Immunohistochemical analysis was performed on human CRAC and adenoma for the mTOR signaling components, including mTOR, phosphorylation, and activation of S6 kinase (p70-S6K), S6 ribosomal protein (S6), and eukaryotic initiation factor 4E-binding protein (4EBP1). A total of 100 cases with colorectal adenocarcinoma (CARC; N=40), adenoma with high-grade intraepithelial neoplasms (HIN; N=30), and adenoma with low-grade intraepithelial neoplasms (LIN; N=30) were enrolled in this study. p-mTOR expression was observed in 30 cases of the CRAC tissues (75%), 9 cases of adenoma with HIN (30%), and 2 cases of adenoma with LIN (7%). In addition, p-S6 expression was observed in 22 cases of CRAC tissues (55%), 8 cases of adenoma with HIN (27%), and 3 cases of adenoma with LIN (10%). A significant correlation was observed among the p-mTOR, p-S6 expression, and the adenoma–carcinoma sequence. Interestingly, the p-S6 protein was activated more in early CRAC than in advanced CRAC.
참고문헌 (19)
- Brown EJ, "A mammalian protein targeted by G 1-arresting rapamycin-receptor complex", Nature, 369(6483), pp.756~758 (1994)
- Kim, DH, "mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery", Cell, 110(2), pp.163~176 (2002)
- Hermsen M, "Colorectal adenoma to carcinoma progression follows multiple pathways of chromosomal instability", Gastroenterology, 123(4), pp.1109~1119 (2002)
- Jackman RJ, "The adenoma-carcinoma sequence in cancer of the colon", Surg Gynecol Obstet, 93(3), pp.327~330 (1951)
- Nagel R, "Regulation of the adenomatous polyposis coli gene by the miR-135 family in colorectal cancer", Cancer Res, 68(14), pp.5795~5802 (2008)
- Toll AD, "Prognostic significance of high-grade dysplasia in colorectal adenomas", Colorectal Dis, 13(4), pp.370~373 (2011)
- Brenner H, "Protection from colorectal cancer after colonoscopy", Ann Intern Med, 154(1), pp.22~30 (2011)
- Mamane Y, "mTOR, translation initiation and cancer", Oncogene, 25(48), pp.6416~6422 (2006)
- Tee AR, "mTOR, translational control and human disease", Semin Cell Dev Biol, 16(1), pp.29~37 (2005)
- Noh WC, "Activation of the mTOR signaling pathway in breast cancer and its correlation with the clinicopathologic variables", Breast Cancer Res Treat, 1109(3), pp.477~483 (2008)
- No JH, "Activation of mTOR signaling pathway associated with adverse prognostic factors of epithelial ovarian cancer", Gynecol Oncol, 121(1), pp.8~12 (2011)
- Faivre S, "Current development of mTOR inhibitors as anticancer agents", Nat Rev Drug Discov, 5(8), pp.671~688 (2006)
- Fingar DC, "Mammalian cell size is controlled by mTOR and its downstream targets S6K1and 4EBP1", eIF4E, 2002, pp.16(12), 1472~1487
- Brown EJ, "Control of p70 s6 kinase by kinase activity of FRAP in vivo", Nature, 377(6548), pp.441~446 (1995)
- Burnett PE, "RAFT1 phosphorylation of the translational regulators p70 S6kinase and 4E-BP1", Proc Natl Acad Sci, 95(4), pp.1432~1437 (1998)
- Gingras AC, "Regulation of 4E-BP1 phosphorylation: A novel two step mechanism", Genes Dev, 13, pp.1422~1437 (1999)
- Inoki K, "Signaling by target of rapamycin proteins in cell growth control", Micro Mol Biol Rev, 69(1), pp.79~100 (2005)
- Lazaris-Karatzas A, "Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA cap", Nature, 345(6275), pp.544~547 (1990)
- Graff JR, "Reduction of translation initiation factor 4E reduces tumor growth, invasion and metastasis of ras transformed cloned rat embryo fibroblast", Int J Cancer, 60(17), pp.255~263 (1995)
