Telomere shortening occurs early during gastrocarcinogenesis
Tóm tắt
When telomeres are shortened to a critical length, they will initiate chromosomal instability (CIN) and may finally cause tumorigenesis. The purpose of the present study was to evaluate the shortened telomere as a potential biomarker for tumorigenesis in gastric carcinoma. The telomeres in matched cancer and adjacent noncancer mucosa samples from 86 gastric carcinoma patients were measured by real-time polymerase chain reaction (PCR). According to the International Union Against Cancer (UICC), tumor stages were classified into four groups: stage I (n = 23), stage II (n = 20), stage III (n = 23), and stage IV (n = 20). Telomere length decreased with aging in both adjacent noncancer mucosa and cancer tissue (r = −0.261 (P = 0.008) and r = −0.27 (P = 0.012), respectively). The telomere length of UICC stage I tumors was significantly shorter than the average telomere length in adjacent noncancer mucosa (P = 0.023). Telomere length increased gradually with increasing UICC stage (P = 0.032). The telomere length of UICC stage IV tumors was significantly longer, when compared to that in noncancer mucosa (P = 0.019) and stage I tumors (P = 0.002). In summary, telomere length undergoes shortening in early stage gastric carcinoma and lengthening in advanced gastric carcinoma. Additionally, telomere shortening may initiate the tumorigenesis of gastric carcinoma.
Tài liệu tham khảo
Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ. Gastric cancer. Lancet. 2009;374(9688):477–90.
Catalano V, et al. Gastric cancer. Crit Rev Oncol Hematol. 2009;71(2):127–64.
Milne AN, Carneiro F, O’Morain C, Offerhaus GJ. Nature meets nurture: molecular genetics of gastric cancer. Hum Genet. 2009;126(5):615–28.
Tahara E. Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol. 1993;119(5):265–72.
Bornschein J, Kandulski A, Selgrad M, Malfertheiner P. From gastric inflammation to gastric cancer. Dig Dis. 2010;28(4–5):609–14.
Chin L, et al. p53 deficiency rescues the advance effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999;97(4):527–38.
Aida J, et al. Telomere length variations in 6 mucosal cell types of gastric tissue observed using a novel quantitative fluorescence in situ hybridization method. Hum Pathol. 2007;38(8):1192–200.
Sobin LH, Wittekind CH. TNM classification of malignant tumors. 6th ed. New York, NY, USA: Wiley; 2002.
Canela A, Klatt P, Blasco MA. Telomere length analysis. Methods Mol Biol. 2007;371:45–72.
Cawthon RM. Telomere measurement by quantitative PCR. Nucleic Acids Res. 2002;30(10):e47.
Blackbum EH. Structure and function of telomeres. Nature. 1991;350:569–73.
Djojosubroto MW, Choi YS, Lee HW, Rudolph KL. Telomeres and telomerase in aging, regeneration, and cancer. Mol Cells. 2003;15(2):164–75.
Furugori E, et al. Telomere shortening in gastric carcinoma with aging despite telomerase activation. J Cancer Res Clin Oncol. 2000;126(8):481–5.
Nakamura K, et al. Correlation of telomere lengths in normal and cancers tissue in the large bowel. Cancer Lett. 2000;158:179–84.
Gumus-Akay G, et al. Telomerase activity could be used as a marker for neoplastic transformation in gastric adenocarcinoma: but it does not have a prognosyic significance. Genet Mol Res. 2007;6(1):41–9.
Nakamura Y, Tahara E, Tahara H, Yasui W, Ide T. Quantitative reevaluation of telomerase activity in cancerous and noncancerous gastrointestinal tissues. Mol Carcinog. 1999;16(4):312–20.
Liu XN, et al. Constitutive telomere length and gastric cancer risk: case–control analysis in Chinese Han population. Cancer Sci. 2009;100(7):1300–5.
Blackburn EH. Telomeres and telomerase: their mechanism of action and the effects of action and the effects of altering their functions. FEBS Lett. 2005;579:859–62.
Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. J Mol Biol. 1992;225(4):951–60.
Artandi SE, et al. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature. 2000;406:641–5.
Cosme-Blanco W, Chang S. Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis. Exp Cell Res. 2008;314:1973–9.
Gertler R, et al. Telomere length and human telomerase reverse transcriptase expression as markers for progression and prognosis of colorectal carcinoma. J Clin Oncol. 2004;22:1807–14.
Kim NW, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011.