Obviously, tissue-specific. Mice KSP Inhibitors M atm Have p53-dependent Independent Apoptosis in the lymphatic tissue adversely Chtigt Irradiated and development of the central nervous system to wild-type M Nozzles 2, 20, 51 compared. But after a short delay Gerung, the induction of p53 and apoptotic responses largely intact in the epithelial cells of the hair follicles and intestinal crypts of ATM-null M Irradiated use 17th This is a role playing atm Loan in apoptosis St essential DNA-Sch In the lymphocytes Of, but there are alternative ways in epithelial tissues, which may compensate in the absence of ATM. The presence of DNA-beautiful-ended ligand redundant signaling pathways in specific tissues, such as epithelial explained Ren narrow spectrum of tumors in Atm-deficient M Mice was observed.
Is a longstanding issue for the model where the DNA is Sch Ending a selective pressure against p53, the source of the DNA-Sch Tion damage tumors. Several recent studies have shown that L pr Kanzer sen sions of human DNA are constitutively active signaling Sch as determined by staining for F-H2AX γ, activated ATM, CHK-2, p53, and 4; 16th He also showed that Tandutinib oncogenes such as Ras k Can DNA-Sch The signaling and Atm, the loan will be St induce k Can p53-mediated senescence and tumor suppression 5, 12. Here we test the r The jaw joints may need during the tumor progression by comparing the effects of ATM and the loss of p53 in epithelial and lymphoid Of tumor models. Results initially we check How to output R The ATM in the suppression of Ras-driven tumors, by testing the sensitivity of ATM-deficient M Nozzles to DMBA / TPA-induced skin tumors.
This protocol includes the topical application of DMBA carcinogenic on the skin of the back, twice w Followed weekly applications of TPA tumor promoter. This induces benign squamous papilloma, a small percentage of what is developing m for may have to b Sartige Epidemo cancer After a long period of latency. Mutation of the HRC is the foreign Send event in this tumor model and in about 90% of both papillomas and carcinomas detected 39. Mutation analysis of p53 inactivation occurs sp t and is strongly associated with the conversion of papilloma-carcinoma to 7. A r The pathogen p53 in the malignant progression was based on the germline knockout M Nozzles of the p53 gene which showed a significantly accelerated rate of formation carcinoma 26th That mutations in p53 are HRAS and Bailey et al.
Page 2 Mol Cancer Res author manuscript in PMC 2009 1 July. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript reproducibly at specific stages in this model facilitates the evaluation of the interaction of ATM with cancer genes in the indigenous development of tumors. 100% of the DMBA / TPA-treated Atm + / +, Atm + / and atm Mice developed papillomas, which first appeared between 7 � Weeks after DMBA treatment. The average number of papillomas per mouse was Similar for all genotypes through 25 weeks of observation. The growth rate of papillomas, as tumor size S was measured, was it Similar for all genotypes to 15 weeks, but slightly in ATM-null M Mice decreased after 15 weeks.
Carcinomas first appeared in Atm + / +, Atm + / and atm Mouse 15, 22 and 25 weeks, respectively. The latency period for the formation of carcinomas of Kaplan-Meier curves shown in Figure 1C. The median age for the development of carcinoma was 29, 32 and 27 weeks for Atm + / +, Atm + / and atm Mice that were, respectively, and these values are not significantly different. But w Died during this study, many ATM-null Mice of lymphoma, and some of them died before a realistic chance of progression of carcinomas. Therefore, we have also analyzed the frequency conversion of papillomas to carcinomas of M Mice that lived at least 20 weeks after DMBA. Table 1 shows the percentage of carcinomas, papillomas which had progressed 5.6%, 8.3% and 5.0% in Atm + / +, Atm + / And atm M to investigate Mice. This s