Single nucleotide polymorphism in ATM and non-small cell lung cancer susceptibility / 中国癌症杂志

Background and purpose: The ataxia-telangiectasia mutated (ATM) gene results in ataxia-telangiectasia (A-T) and it is closely associated with tumors. ATM is an important signal transducer that is involved in the repair of DNA double-strand break damage by phosphorylating numerous target proteins . This study was aimed to investigate the correlation between a single nucleotide polymorphism (SNP) in ATM gene (IVS62+60G>A) and the risk of non-small cell lung cancer(NSCLC) in a case-control study. Methods: From June 2004 to December 2005, a total of 264 patients with NSCLC were recruited, 264 healthy people as control. All of specimens were collected from Zhejiang Tumor Hospital. DNA was extracted from peripheral blood and then was used to determine. ATM genotype by Taqman SNP genotyping assays. Logistic regression model was employed to analyze the relationship between SNP and NSCLC risk. Results: The percentage of NSCLC patients in 86 patients with A/A genotype, 139 patients with A/G and 39 patients with G/G were 32.6% (86/264), 52.6% (139/264), 14.8% (39/264), respectively. The percentage in 68 healthy people with A/A genotype, 139 healthy people with NG and 55 healthy people with G/G were 26.0% (68/262), 53.0% (139/262) and 21.0% (55/262), respectively. The proportion of G/G genotype in 264 patients was obviously lower than that in the 264 healthy control (14.8% vs 21.2%, P<0.05). The people with G/G genotype had lower risk to NSCLC than there with A/A genotype (OR=0.561, 95% CI=0.334-0.942, P=0.029). Conclusion: The ATM SNP(IVS62+60G>A)was associated with the NSCLC risk, and homozygous G alleles may be a protective factor to NSCLC.

Changes of the cell cycle regulators and cell cycle arrest in cervical cancer cells after cisplatin therapy / 药物分析学报

Objective To investigate the changes of the cell cycle regulators ATM, Chk2 and p53 and cell cycle arrest in HeLa cells after cisplatin therapy. Methods The proliferation-inhibiting rates of HeLa cells induced by eisplatin of different concentrations were measured by MTT assays. The mRNA and protein expressions of ATM, Chk2 and p53 of HeLa cells with and withont cisplatin were detected by RT-PCR and Western blot, respectively. The cell cycle analysis was conducted by flow cytometric analysis. Results Cisplatin inhibited the proliferation of HeLa cells in a dose- and time-dependent manner. The mRNA and protein expressions of ATM, Chk2 and p53 were increased in HeLa cells treated with cisplatin. The cell cycle was arrested in G2/M phase in HeLa cells treated with cisplatin. Conclusion Activation of ATM, Chk2 and p53 might be critical in determining whether cells survive or undergo apoptesis. Targeting ATM, Chk2 and p53 pathway might he a promising strategy for reversing chemoresistance to clsplatin in cervical cancer.

Changes of the cell cycle regulators and cell cycle arrest in cervical cancer cells after cisplatin therapy / 西安交通大学学报·英文版

Objective: To investigate the changes of the cell cycle regulators ATM, Chk2 and p53 and cell cycle arrest in HeLa cells after cisplatin therapy. Methods: The proliferation-inhibiting rates of HeLa cells induced by cisplatin of different concentrations were measured by MTT assays. The mRNA and protein expressions of ATM, Chk2 and p53 of HeLa cells with and without cisplatin were detected by RT-PCR and Western blot, respectively. The cell cycle analysis was conducted by flow cytometric analysis. Results: Cisplatin inhibited the proliferation of HeLa cells in a dose- and time-dependent manner. The mRNA and protein expressions of ATM, Chk2 and p53 were increased in HeLa cells treated with cisplatin. The cell cycle was arrested in G2/M phase in HeLa cells treated with cisplatin. Conclusion: Activation of ATM, Chk2 and p53 might be critical in determining whether cells survive or undergo apoptosis. Targeting ATM, Chk2 and p53 pathway might be a promising strategy for reversing chemoresistance to cisplatin in cervical cancer.

Advances in research on ATM as a target for novel radiosensitizers / 中国癌症杂志

Patients with ataxia-telangiectasia ( A-T) syndrome were charachaterized by profound hypersensitivity to ionizing radiation in clinic. Many studies have shown that this hypersensitivity possibly attributed to ATM gene whose critical compartment was ATM kinase. So inhibitors of the ATM kinase such as caffeine, pentoxifylline, methyl xanthines and 7-hydroxystaurosporine (UCN-01) were developed and have achieved a few encouraging results in basic and clinical stuides.

Gene mutation in ATM/PI3K region of nasopharyngeal carcinoma cell lines / 中华放射肿瘤学杂志

Objective To define the correlation between nasopharyngeal carcinoma (NPC) cell radiosensitivity and gene mutation in the ATM/PI3K coding region. Methods The gene mutation in the ATM/PI3K region of nasopharyngeal carcinoma cell lines which vary in radiosensitivity,was monitored by reverse transcription polymerase chain reaction (RT PCR) and fluorescence marked ddNTP cycle sequencing technique.Results No gene mutation was detected in the ATM/PI3K region of either CNE1 or CNE2.Conclusion Disparity in intrinsic radiosensitivity between different NPC cell lines depends on some other factors and mechanism without being related to ATM/PI3K mutations.