Ku Protein Expression In Human Lung Cancer Tissue And Clinical Significance

Background: Ku, a heterodimer of KU70 and Ku80, was originallu identified as a majr target of autoantibodies from tatients with scleroderma-polymyositis oberlap syndrome in 1981. Ku,as the regulatory subunit of DNA-dependent protein kinase (DNA-PK), cooperating with the catalytic subunit (DNA-PKcs) constitute DNA-dependent protein kinase, play an important role in DNA double-strand break(DSB) repair. DNA-PK is a nucleonic serine/ threonine protein kinase, composed with catalytic subunit and regulatory subunit; and Ku is the regulatory subunit. Ku bind DNA breakage ends, protecting DNA ends not to be hydrolyzed by exonuclease, and activate the catelytic subunit (DNA-PKcs) to participate in repairing of breaking DNA by Non-homologous end-joining(NHEJ).Ku, majority as neucleoprotein participate many biology biology, beside DNA DSB repair, play an important role in transcription regulation, maintaining the integrity of telomere ends and chromosome, and maintaining cell existing. When a cell subjects to nucleolytic attack and nucleotide loss,heterodimer of KU70 and Ku80 protects telomere ends and avoids end-to-end joining. When one or both subunits of Ku are missing, mammalian cells exhibit a marked increase in chromosomal aberrations, including DNA breakage, translocations, and aneuploidy elevated telomeric fusions , adiation sensitivity and defective V(D)J recombination. Ku deficiency leads to profound growth retardation, and premature senescence. Ku70 and Ku80 mutational mus musculus show IR sensitive and B cell blastocolysis. Now more and more stardies have indicatede that the closely relationshop between Ku and the developing of tumor, prior studies suggest that a delicate balance exists in Ku expression as overexpression of Ku proteins promotes oncogenic phenotypes,including hyperproliferation and resistance to apoptosis,whereas deficient or low expression of Ku leads to genomic instability and tumorigenesis. Studies have confirmed that sensitivity of radiation damage of tumor cells can increase after Ku gene was blocked or knockouted. So research has been more and more payed close attention to Ku, and Ku will become early diagnosis, effect evaluation, judgement prognosis,and especially new hot spot of gene therapy. Our study provid protophase work for these studies.Lung cancer is the most highest morbidity and mortality in the world and infront of tumor case fatality. How to elevate therapeutic effect andsurvival rate of lung cancer has become focal point of clinical treatment. At present, many scientis study reversing resistivity of radiotherapy and chemotherapy with expressing genome and proteome. Previous researches have confirmed that Ku playes an important role in DNA DBS repairing, and Ku expression influence sensitivity of antitumor drug and radiotherapy of tumor. Most srudies indicate that Ku expression in malign tissue was obviously higher nomal tissue and innocence tissue. Ku expression gradually increases coupled with increasing of malign extent of tumor .Because of disparity sample size and investigate method, the relation between Ku expression in different tissue and malign extent and molecule mechanism of Ku in the process of tumorigenesis and development do not indentify. Our study first detected Ku7 and Ku80 protein expression in nomal human lung tissue, lung cancer(small-cell lung cancer tissue ,adenous cancer, prickle cell carcinoma),in order to identufy if Ku protein expression in nomal human lung tissue, lung cancer is significant deviation and approach the relationship between Ku protein expression and sensitivity of chemotherapy and radiotherapy, clinical stage, distant diversion of lung cancer. Further elucidating Ku quantitation expression is very significant for early diagnosis, progression, prognosticating sensitivity of chemotherapy and radiotherapy of tumor. Our study may provide new way that resistivity of chemotherapy and radiotherapy and provide theory support of choose, practice individualization antineoplaston.Experiment purpose: Compareing expression protein Ku in normal lung tissue and different tissue typing lung cancer, we will elucidate the significance of clinical diagnosis and therapeutics of expressing Ku70/86 in lung cancer.Experimental methods: Expression of Ku70/86 in 30 normal lung tissueand 72 lung cancer samples were measured by immunohistochemistry (enzyme linked immunosorbent assay). The number of cells in tumor samples stained positive for Ku70 and Ku86 was recorded by scoring ten microseecope fields of 100 tumor cells by one secialty patho-experiment member and author of this dissertation. In tumor tissue, The number of cells which stained positive for Ku70 and Ku86 was recorded. Recorded the averages of tow person.Experimental results:(1) Ku70 and Ku80 protein express both in group of normal lung tissue and each type lung cancer,and extent of expression in these group were different. (2) Expression of Ku70 and Ku80 protein in nonsmall-cell lung cancer tissue (adenous cancer, prickle cell carcinoma) was obviously higher than small-cell lung cancer and normal lung tissue. The difference is of significance in statistics science. (3) Increasing of Ku70 protein expression in lung cancer tissue connected with progression of stages of lung cancer,that analyses displayes norientation linear correlation between them. Ku70 protein expression in distant place (IV ) lung cancer tissue and non- distant place (I-III) lung cancer tissue had statistic significant meaning,p<0.05. But Ku80 didn't had these tow analyses tatistic meaning.(4) Ku70 and Ku80 protein didn't had dependability with age and sex.Experimental conclusion: (1) Extent of Ku protein expression in group of normal lung tissue and each type lung cancer were different . That indicates Ku, as DNA binding protein in cells, was reside in both tumor and normal cells, that maybe because of different extent of DNA proliferation, damage repairing, Ku protein expression is also different. (2) Expression of Ku protein in nonsmall-cell lung cancer tissue (adenous cancer, prickle cell carcinoma) was obviously higher than small-cell lung cancer and normal lung tissue. Ku70/80 expression concerned with DNA repairing capability in different histotype tumor cell, that maybe one of molecule mechanism of nonsmall-cell lung cancer, specially adenous cancer, has resistivity of radiotherapy and chemotherapy. There is important meaning in aearly discovery, treatment and evaluate prognosis. (3) Between Ku70 expression in lung cancer and progression of stages of lung cancer,there is norientation linear correlation. Ku70 protein expression in distant place (IV ) lung cancer tissue and non- distant place (I-III) lung cancer tissue had statistic significant meaning. That indicates that increasing of Ku70 expression concerned with the increasing of progression, extent of malignant of tumor cell. Ku protein contains tow subunits,Ku70 and Ku80.They have independent biological function. (4) Ku70 and Ku80 protein didn't had dependability with age and sex. Ku, as biosystem's imperative function protein, educes effective and does not influence with age and sex. Ku quantitation expression may become new target of early diagnosis, monitoring resistivity of radiotherapy and chemotherapy judgement prognostic. Our study establishes foundation of gene therapy of Ku promoting apoptosis and reversing resistivity of radiotherapy and chemotherapy.