Down-Modulation of Notch1 Expression in Cervical Cancer Is Associated with HPV-Induced Carcinogenesis

OBJECTIVE Notch1 signaling has been implicated intumorigenesis. The purpose of this study was to investigate theputative role of the Notch1 receptor in carcinogenesis and in theprogression of the cervical cancer. Since human papillomavirus(HPV) is a causative agent in cervical carcinoma, the interactionbetween Notch1 and HPV infection was examined.METHODS Forty cervical cancer samples and 30 normalcervical tissue specimens were examined using Western blot andRT-PCR to detect Notch1 protein and mRNA levels. HPV16 DNAwas examined in all samples using PCR.RESULTS The level of Notch1 protein expression wassignificantly lower in cervical cancer tissue than in normal tissue.Levels of Notch1 mRNA were found to be substantially downregulatedin cancer tissue. Notch1 protein expression levelswere significantly higher in carcinomas without HPV DNAthan that in carcinomas with HPV infection (55.5% vs. 3.3%, P <0.05). Down-modulation of Notch1 mRNA levels in carcinomawas demonstrated to be associated with HPVE6 transcription.Moreover, levels of Notch1 expression were shown to besignificantly higher in early stage disease than in advanced stagedisease (P = 0.001).CONCLUSION Down-modulation of Notch1 expressionprobably plays an important role in the late stages of HPVinducedcervical cancer.

辐射生物效应研究——低剂量率长时间持续照射的潜在危险

本文介绍了近年来关于低剂量率长时间连续照射生物效应研究的某些进展,指出了低剂量率长时间持续照射对人类健康的潜在危险,同时也指出了各类核设施常规剂量监测的重要性,应当引起人们的高度重视.

Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice

Objective： To investigate the enhancive effect ofN, N′-dinitrosopiperazine （DNP） on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN（p53mt-LMP1）/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma （NPC）. Methods： TgN（p53mt-LMP1）/HT transgenic mice and the same strain of C57BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN（p53mt-LMP1）/HT cancerous lesion-inducing group （T1）, TgN（p53mt-LMP1）/HT control group （TC）, C57BL/6J cancerous lesion-inducing group （CI）, and C57BL/6J control group （CC）. TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls.At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by hacmatoxylin and eosin （HE） staining and for determination on the expression ofTRAF2, c-Jun, and p 16 by immunohistochemistry. Results： Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 （P〈0.01） respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-0-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor （TNF） receptor-associated factor 2 （TRAF2） and c-Jun in these samples were significantly up-regulated in TI （P〈0.0 I）, while tbe expression of p16 was significantly lower in TI than in the other groups （P〈0.01）. Conclusion： TgN（p53mt-LMPI）/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN（p53mt-LMP1）/HT mice should be closely associated with abnormal signaling of activator protein-1 （AP-1） pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p l6.