MEN1 deficiency leads to neuroendocrine differentiation of lung cancer and disrupts the DNA damage response.

The MEN1 gene, a tumor suppressor gene that encodes the protein menin, is mutated at high frequencies in neuroendocrine (NE) tumors; however, the biological importance of this gene in NE-type lung cancer in vivo remains unclear. Here, we established an ATII-specific KrasG12D/+/Men1-/- driven genetically engineered mouse model and show that deficiency of menin results in the accumulation of DNA damage and antagonizes oncogenic Kras-induced senescence and the epithelial-to-mesenchymal transition during lung tumorigenesis. The loss of menin expression in certain human primary lung cancers correlates with elevated NE profiles and reduced overall survival.

[Induction effects of pentachlorophenol on vitellogenin and p53 in Chinese rare minnow (Gobiocypris rarus)].

Taking the Chinese rare minnow (Gobiocypris rarus) as the test animal, the studies were designed to investigate induction effects of pentachlorophenol (PCP) on vitellogenin (VTG) protein, VTG gene and tumor suppressor p53 gene in the liver of Gobiocypris rarus. The endocrine disrupting of PCP was evaluated by detecting VTG, and sensitive biomarkers of PCP were screened at both protein and mRNA levels. Gobiocypris rarus were exposed to PCP at 1.5, 15, 40, 80, 120, 150, 160 microg x L(-1) respectively, while setting blank, solvent control and 17alpha-ethynylestradiol (EE2) as positive control. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), enzyme-linked immunosorbent assay (ELISA), VTG protein expression differences were detected in the liver of Gobiocypris rarus after exposure to PCP. Cloning the VTG and p53 gene new fragments of Gobiocypris rarus based on conserved regions, mRNA expression levels of VTG and p53 gene in the liver of Gobiocypris rarus were determined by quantitative real-time PCR assay after PCP treatment. The results showed that 40, 80, 120, 160 microg x L(-1) PCP induced the liver of male and female Gobiocypris rarus to produce VTG protein, and had a significant concentration effect. VTG and p53 mRNA levels significantly increased in the liver of Gobiocypris rarus after exposure to 1.5, 15, 150 microg x L(-1) PCP, and had remarkable concentration and time effects. The studies suggested that PCP had estrogenic effects, and VTG protein, VTG and p53 gene in the liver of Gobiocypris rarus could be used as candidate sensitive biomarkers for detecting PCP.

[Effects of pentachlorophenol on DNA damage and cytotoxicity of HeLa cells].

Using human cervical carcinoma HeLa cells, the cell viability was determined by MTT assay after pentachlorophenol (PCP) treatment, the cytotoxicity of PCP was evaluated by detecting lactate dehydrogenase (LDH) leakage rate and total superoxide dismutase (SOD) activity in cell culture medium; DNA damage was detected by comet assay. The results indicated that HeLa cells proliferation was inhibited by PCP and the median inhibitory concentration (IC50) was 66.59 micromol x L(-1); PCP did not induce DNA damage in the concentration range from 6.25 micromol x L(-1) to 50 micromol L(-1); LDH leakage rate increased gradually with the increasing of exposure time when HeLa cells were treated by PCP in the concentration range from 12.5 micromol x L(-1) to 200 micromol x L(-1); SOD activity decreased gradually as the increasing of exposure time when HeLa cells were treated by PCP at lower concentration of 12.25 micromol x L(-1), 17.5 micromol x L(-1), 25 micromol x L(-1) respectively, LDH leakage rate increased significantly at 25 micromol x L(-1) and activity of SOD decreased markedly at 12.25 micromol x L(-1) in HeLa cells following PCP-treatment respectively. Results suggested that SOD and LDH might be regarded as candidate sensitive biomarkers for evaluating toxicity of PCP at low concentration on human and wildlife.