| The mechanism of ionization radiation induced carcinogenesis remains to know. To elucidate the mechanism of radiation carcinogenesis will help us to effective prevention and better treatment for carcinomas. Former studies have demonstrated that the initiation of irradiation induced carcinogenesis, just like carcinomas induced by other carcinogens, is correlated with tumor related genes such as oncogene, tumor-suppressor gene and cell cycle mediating gene. Alterations of these tumor-related genes are key molecular events during the process of carcinogenesis.MDM2 (murine double minute) gene is an oncogene coding a 90 kd protein. MDM2 can form different variants via alternative slicing of mRNA such as p57, p64, p85, p90. As a down-stream factor of p53, MDM2 can mediate P53 network, degrading P53 via ubiquitin-proteasome pathway and participating in modulation of cellular proliferation, division, cell cycle and apoptosis. MDM2 and P53 formed degradation/transactivation circle: MDM2can degrade the P53protein; While P53 can transactivate the expression of MDM2, eliminating the feedback. P53/MDM2 mode is the classic mode for interaction of oncoprotein/tumor-suppressor [1]. The interaction between P53 and MDM2 is the key point of the 2 automatic feedback loops of P53: -lactanine loop and KT/PKB loop. And destroy of balance of p53\mdm2 is considered to be relative to development and progress of malignancies. The p53/MDM2/P14ARF signal pathway is one of the most important cell cycle mediating pathways in humancarcinomas. Most of adenocarcinomas are found alterations of p53/MDM2 pathway, and overexpression of MDM2 has direct oncogenic tendency.The overexpression of MDM2 mRNA was found closely related to metastasis of nasopharyngeal carcinoma (NPC) to lymph nodes of neck; and MDMD2 protein level of metastasis cervix carcinoma was higher than that in intraepithelial carcinoma or precancerous lesion; in the carcinoma of testis, the MDM2 level was increased with the transferability and the clinical grade. In short, MDM2 expression level can signify the clinical progress of carcinoma, and MDM2 level is correlated with the proliferation and metastasis of carcinoma.MDM2 overexpression was found negatively correlated with the sensibility of radiotherapy, which may result in the low survival rate of adult medulloblastoma. Therefore, the MDM2 level has instruction significance and might become a effective clinical marker to predict the prognosis .Wang H used the anti-sense MDM2 oligonucleotide to suppress the expression of MDM2 to treat the colon carcinoma and polymorphism glial carcinoma, and study the therapeutic effects antisense nucleotides. The investigation showed that the antisense nucleotides could effectively inhibit the growth of tumor and enhanced the effects of chemical drugs.P73 gene is a member of p53gene family, containing 14 exons and 13 introns. P73 mRNA can form splicing variants . P73 can bind with classic P53 substrates and activate P53 target gene such as p21 gene and MDM2 gene, thus mediating the cell proliferation, cell cycle and apoptosis[3, 5].Recent studies found, however, p73 was of great difference compared with p53. It is seldom mutated and frequently overexpressed in various carcinomas such as ovary carcinoma, esophageal carcinoma,and melanoma etc. only in special carcinoma such as T lymphocyte lymphoma, p73 is down-regulated due to methylation of CpG island. The overexpression of p73 can suppress the proliferation of p53 (-/-) cell, and promote cell to death or apoptosis. Fuchssy[27] transfected the wild-type human p73 to ovary carcinoma cell to find that transcription activity of endogenic p53 greatly decreased, thus overexpression of p73 may one of mechanisms of p53 passivation.In mammalian cells, depletion of P73C terminal can enhance the function of DNA binding and transactivation, but decrease the activity of inducing apoptosis. It suggests that the difference of C terminal contribute to different functions of protein, and further investigation of p73 variants can help us to bet... |
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