Insan Glioma Hücre Dizilerinde Telomeraz Aktivitesi ve Siyalik Asit

Amaç: Telomeraz enzim kompleksi, diğer proteinlerin yanında, TERT ve TR olmak üzere iki temel subunitten oluşur. Polisiyalik asit zincirleri muhtemelen hücrelerin birbirlerine daha kolay yapışmasını sağlayarak, NCAM moleküllünün adeziv fonksiyonunu düzenler. Telomeraz aktivitesi ve siyalik asit düzeyleri gliomaların biyolojik davranışlarını belirlemede kullanılabilir. Gereç ve Yöntem: İnsan glioma hücre dizilerinden elde edilen hücre ekstraktlarında, telomeraz aktivitesi ve siyalik asit düzeyleri araştırıldı. Telomeraz aktivitesini belirlemek için, telomerik tekrar amplifikasyon protokolü uygulandı. Siyalik asit düzeylerini ölçmek için, siyalik asit kiti kullanıldı. Hücre dizisinde hTERT, hTR ve GADPH ekspresyonları RT-PCR kiti kullanılarak belirlendi. NCAM için, flask tabanında fikse edilen hücrelerde streptavidin-biotin peroksidaz boyama metodu uygulandı. Bulgular: İnsan glioma hücre dizilerinin sonraki pasajlarında telomeraz aktivitesi her ne kadar dalgalı olsada artmış olarak bulundu. Telomeraz RNA’sı ve TERT ekspresyonları tüm pasajlarda pozitifti. Siyalik asit düzeyleri de artış gösterdi ve bu artış insan glioma hücre dizilerinin ilerleyen pasajlarında düzenliydi. NCAM molekülü tüm pasajlarda pozitif olarak bulundu. Sonuç: Başlangıçta ilerleyen pasajlarda artması beklenen telomeraz aktivitesi dalgalı olarak artmıştır. Bunun yanında glioma hücre dizilerinin ilerleyen pasajlarında siyalik asit düzeyleri daha düzenli artış göstermektedir

Anahtar Kelimeler:

DK-MG hücre dizisi, siyalik asit, telomeraz aktivitesi, hTERT, hTR, NCAM

Telomerase Activity And Sialic Acid Levels In Human Glioma Cell Lines

Keywords:

-,

PDF

___

Chatziantoniou VD: Telomerase: Biological function and potential role in cancer management. Pathol Oncol Res 7: 161-170, 2001 .
Colgin M.L., Reddel R.R.: Telomere maintenance mechanisms and cellular immortalization. Current Opinion in Genetics & Development, 9: 97-103, 1999.
Lingner J., Cech T. R.: Telomerase and chromosome end maintenance, Current Opinion in Genetics & Development, 8:226-232, 1998.
Morii K., Tanaka R., Onda K., Tsumanuma I., Yoshimura J.: Expression of telomerase RNA, telomerase activity, and telomere length in human gliomas. Biochemical and Biophysical Research Communications, 239, 830-834, 1997.
Shay, J.W., Wright, W.E.: Telomerase activity in human cancer. Current Opinion in Oncology, 8:66- 71, 1997.
Fukushima T, Yoshino A, Katayama Y, Kusama K, Moro I: Prediction of clinical course of diffusely infiltrating astrocytomas from telomerase expression and quantitated activity level. Cancer Lett 187: 191- 198, 2002.
Harada K, Kurisi K, Tahara H, Ide T, Tahara E: Telomerase acticity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker. J Neurosurg 93: 618-625, 2000.
Huang F, Kanno H, Yamamoton I, Lin Y, Kuboto Y: Correlation of clinical features and telomerase activity in human gliomas. J Neuro Oncol 43: 137- 142, 1999.
Kleinschmith-demaster BK, Evans LC, Bobak JB, Lopez-Uribe D, Hopper D, Shroyer AL, Shroyer KR: Quantitative telomerase expression in glioblastomas shows regional variation and down-regulation with therapy but no correlation with patiant outcome. Hum Pathol 31: 905-913, 2000.
Shervington A, Cruickshanks N, Wright H, Atkinson- Dell R, Lea R, Roberts G, Shervington L: Glioma: What is the role of c-Myc, hsp90 and telomerase? Mol Cell Biochem 283: 1-9, 2006.
Holzmann K, Berger W, Mejri D, Cerni C, Sasgary S: Detection and quantification of transcript for the catalytic subunit TERT and the RNA component of telomerase in rat tissue. Anal Biochem 317: 120-123, 2003.
Komata T, Kondo Y, Kanzawa T, Hirohata S, Koga S, Sumiyoshi H, Srinivasula SM, Parna BP, Germano IM, Takakura M, Inoue M, Alnemri ES, Shay JW, Kyo S, Kondo S: Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (human telomerase reverse transcriptase) gene promoter. Cancer Res 61: 5796-5802, 2001.
Nakamura T.M., Morin G.B., Chapman K.B., Weinrich S.L., Andrews W.H., Lingner J., Harley C.B., Cech T.R.: Telomerase catalytic subunit homologs from fission yeast and human. Science. 15; 277(5328):955-9, 1997.
Shore, D.: Telomerase and Telomere–binding Proteins: Controlling the Endgame, TIBS, 22:233-5, 1997.
Wang L, Wei Q, Wang LE, Aldape KD, Cao Y, Okcu MF, Hess KR, El-Zein R, Gilbert MR, Woo SY, Prabhu SS, Fuller GN, Bondy ML: Survival prediction in patient with glioblastoma multiforme by human telomerase genetic variation. J Clin Oncol 24: 1627-1632, 2006.
You Y, Pu P, Huang Q, Xia Z, Wang C, Wang G, Yu C, Reed E, Li QQ: Antisense telomerase RNA inhibits the growth of human glioma cells in vitro and in vivo. Int J Oncol 28: 1225-1232, 2006.
Alberts B., Bray D., Lewis J., Raff M., Roberts K., Watson J.D.: Molecular Biology of the Cell, Third edition, Gurland Publishing, Inc. New York, London, 1994.
Darnell J., Lodish H., Baltimore D.: Molecular Cell Biology, Scientific American Books, Inc., 1990.
Fischer F., Egg G.: n-acetylneurominic acid (sialic acid) as a tumor marker in head and neck cancers. HNO, Oct; 38(10): 361-3, 1990.
Yamamoto H, Saito T, Kaneko Y, Kersey D, Yong VW, Bremer EG, Mkrdichian E, Cerullo L, Leestma J, Moskal JR: 2,3-Sialyltransferase mRNA and
,3-linked glycoprotein sialylation are increased in
malignant gliomas. Brain Res 755: 175-179, 1997.
Marth E, Flaschka G, Stiegler S, Mose JR: Sialic acid as a marker for differentiation between benign and malignant intracranial tumors. Clin Chem Acta 176: 251-257, 1988.
Sonmez H, Kokoglu H, Suer S, Ozyurt E: Fibronectin and sialic acid levels in human meningiomas and gliomas. Cancer Lett 90(2): 119-122, 1995.
Suzuki M, Suziki M, Nakayama J, Suziki A, Angata K, Chen S, Sakai K, Hagihara K, Yamaguchi Y, Fukuda M: Polysialic acid facilitates tumor invasion by glioma cells. Glycobiology 15: 887-894, 2005.
Charter W.N., Mahal L.K., Koshland D.E., Bertozzi C.R.: Differential effects of unnatural sialic acids on the polysialylation of the neural cell adhesion molecule and neural behavior. The Journal of Biological Chemistry, Vol 277, No 11, Issue March 15 pp. 9255-9261, 2002.
Cosan TE: Total sialic acid decrease in the periventricular area of infantile rats with hydrocephalus. Child’s Nerv Syst 19: 829-830, 2003 (comment).
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay CW: Specific association of human telomerase activity with cell and cancer. Science 266: 2011-2015, 1994.
Nakano K, Watney E, Mc Dougall JK: Telomerase activity and expression of telomerase RNA component and telomerase catalytic subunit gene in cervical cancer. Am J Pathol 153: 857-864, 1998.
Shay J.W., Bacchetti S.: A survey of telomerase activity in human cancer. Eur J Cancer 33(5): 787- 791, 1997.
Wynford-Thomas D.: Cellular senescence and cancer. Journal of pathology, 187:100-111, 1999.
Inoue H., Tsuchida A., Kawasaki Y., Fujimato Y., Yamasaki S., Kajiyama G.: Preoperative diagnosis of intraductal papillary-mucinous tumors of the pancreas with attention to telomerase activity. Cancer, 91: 35- 41, 2000.
Hiyama E., Saeki T., Hiyama K., Takashima S., Shay J.W., Matsuura Y., Yokoyama T.: Telomerase activity as a marker of breast carcinoma in fine- needle aspirated samples. Cancer Cytopathology, 90: 235-8, 2000.
Kyo S., Kanaya T., Ishikava H., Ueno H., Inoue M.: Telomerase activity in gynecological tumors. Clinical Cancer Research, Vol 2, 2023-2028 December, 1996.
Murakami J., Nagai N., Ohama K., Tahara H., Ide T.: Telomerase activity in ovarian tumors. Cancer, 80: 1085-92, 1997.
Tomoda R., Seto M., Tsumuki H., Iida K., Yamazaki T., Sonoda J., Matsumine A., Uchida A.: Telomerase activity and human telomerase reverse transcriptase mRNA expression are correlated with clinical aggressiveness in soft tissue tumors. American Cancer Society, 1127-1133, April 2002.
Vietor M., Winter S., Groscurth P., Naumann U., Welter M.: On the significance of telomerase activity in human malignant glioma cells. European Journal of Pharmacology, 27-37, 407, 2000.
Shen Z-Y., Xu L-Y, Chen M-H., Shen J., Cai W-J., Zeng Y.: Progressive transformation of immortalized eusophageal epithelial cells. World J. Gastroenterol, 8(6), 976-981, 2002.
Feng J., Funk W.D., Wong S., Weinrich S.L., Avilion A.A., Chiu C., Adams R.R., Chang E., Allsopp R.C., Yu J., Le S., West M.D., Harley C.B., Andrews W.H., Greider C.W., Villeponteau B.: The RNA component of human telomerase, Science, 269: 1236- 1241, 1995.
Soder A.I., Hoare S.F., Muir S., Going J.J., Parkinson E.K., Keith W.N.: Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer. Oncogene, 14, 1013-1021, 1997.
Canoruç N., Canoruç F., Özden T., Şen C., Değertekin H., Göral V., Ayyildiz O.: Gastrointestinal sistem kanserlerinde sialik asit ve alkalen fosfatazın serum düzeyleri ve tanıdaki önem- leri. Gastroenteroloji, 4(4): 656-660, 1993.
Isitmangil T., Isitmangil G., Budak Y., Aydilek R., Çelenk M. K.: Comparison of serum and bronchoalveolar lavage fluid sialic acid levels between malignant and benign lung diseases. BMC Pulmonary Medicine, pg. 1-5, 2001.
Öktem F., Toprak M., Yazıcılar O., Öz F., Ada M.: Larinks kanserlerinde sialik asit değişimleri. Türk Otolarengoloji Arşivi, 37(3-4): 98-104, 1999.
Bhatavdekar J.M., Patel D.D., Vora H.H., Balar D.B. Squamous cell carcinoma antigen and protein-bound sialic acid in the management of head and neck cancer. Int. J. Biol Markers, Oct-Dec; 6(4): 237-40, 1991.
Uslu E., Belce A., Seymen P., Kökoğlu E.: Kolorektal kanserde metastazın serum total siyalik asit düzeyleri üzerine etkisi, Cerrahpaşa J. Med. 2000;31(4): 231- 234.