HGM2002 Poster Abstracts: 8. Disease Mechanisms
POSTER NO: 449
Study on Expression of hTERT Gene in Laryngeal Carcinoma
Guangbin Qiu, Kailai Sun, Weineng Fu
Telomeres are specialized structures at the ends of eukaryotic chromosomes and consist of hundreds to thousands of tandem repeats of DNA sequence. Telomeres protect the chromosomes from DNA degradation, end-to-end fusion, rearrangements, and chromosomes loss. In the mitosis of normal somatic cells, telomeric DNA may be lost gradually because of 'end replication problem', which results in cells aging or senescence. Tumor cells, however, can maintain the lengths of telomeres by activation of telomerase and then get the ability of indefinite cell divisions, developing to cancers at last. It is showed that telomerases are positive in 85 percent to 95 percent of malignant tumor cells or tissues, but are negative in most normal somatic cells. The relationship among telomere, telomerase and tumor is one of the hot points of cancer research at present. Telomerase is a ribonucleoprotein which consists of three components: human telomerase RNA (hTR), telomerase-associated protein (TP1/TLP) and the catalytic protein subunit of telomerase (hTERT). To the activity of telomerase, hTR functions just as a template, and TP1/TLP helps to the binding between telomerase and telomere, whereas the reverse transcriptase activity of hTERT is the critical factor. Recent studies showed that the level of hTERT mRNA is significantly correlated with telomerase activity. Therefore, detecting the expression levels of hTERT in tumor tissues can reflect telomerase activity directly. In this study, we cloned a fragment of hTERT cDNA into pGEX-4T-2 vector and expressed a fusion protein, which was used to immune the Balb/c mice. By this way, we obtained a strain of monoclonal antibody against hTERT. We performed immunohistochemical staining using this antibody in laryngeal tissues and found that the frequencies of positive cells were very well correlated with clinicopathological parameters and telomerase activity levels. We also demonstrated that the expression of hTERT was positively correlated to the levels of c-myc. These findings revealed that the up-regulation of telomerase activity with degree of undifferentiation in laryngeal cancer tissues was mainly due to the increase in frequency of hTERT positive cells and c-myc may play an important role in activation of telomerase.
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