Equencies were not significantly different using the two-sided Fisher’s exact test � �s. Taken together, these results indicate that ATM deficiency homozygous or hemizygous not significantly improve many Hrasdriven tumor growth rate or malignant progression. In order to compare these results KRN 633 KRN633 to the effects of loss of p53 on the progression of skin tumors, we repeated the protocol of DMBA / TPA-deficient mice to p53 M. We previously reported accelerated malignant progression in p53-deficient mouse germline 26 and here we demonstrate anything similar effects in p53-deficient M Suspended mice with 23. The average number of papillomas was similar in both Trp53F2-10/F2-10; K14-Cre Mice Mice Trp53F2-10/F2-10 compared with 15 weeks. Still seems to be new tumors Be in p53-deficient M Mice after this time, w During the stabilization of the wild species.
The first appearance in Trp53F2-10/F2-10 carcinomas, K14-Cre M Mice at 15 weeks and 30 weeks, 75% of p53-deficient M An average of 2 mice induced tumors in mice M. In contrast, wild-type littermates do not develop tumors after 30 weeks. This difference was highly significant. Thus, the p53 deletion specific Trichostatin A skin dramatically accelerate tumor progression malignant skin, a Hnliches result as in the germline p53 nullizygous M Nozzles 24, 26 observed. What are the effect on the progression of malignant tumor cells inhibit p53 autonomous. Both ATM and p53 skin tumor studies were controlled using The wild-type littermates. This is important because the wild-type mice M From the two studies in cancer-reqs Different susceptibility, probably due to the different genetic backgrounds.
The comparison between these two studies of skin tumors showed that p53 has a more significant effect on the suppression of Ras-driven tumor progression than Atm. Then on the case of DNA-Sch The signaling papillomas was important, and if this ATM-dependent Ngigen p53 expression led. H2AX rapidly in response to DNA double strand breaks 40 and Phospho-H2AX is widely used as a marker of DNA-Sch The phosphorylated used. However γ-H2AX increases in M-phase cells lacking DNA-Sch The can 21, 35 and in epithelial cells are easily may need during the phase of the hair cycle in the skin of untreated M Mice captured 28th The F-H2AX staining on the cell γ was occasionally seen in the hair follicles of normal skin and in the basal and suprabasal cells of papillomas.
Although ATM can phosphorylate H2AX after IR44, we observed Hnliches Ausma to H2AX-F staining in γ papillomas of ATM + / + and Atm � � Mice Indicating that it replaced for ATM kinase k Able to phosphorylate H2AX in vivo. Despite γ H2AX-F Phospho-Chk2 staining, a marker for DNA-Sch The signaling, low or undetectable both ATM + / + and Atm was � � Papillomas. As a contr The positive F Staining for p-Chk2 was seen in irradiated intestinal crypts. p53 is not detectable in normal skin, but significant location in papillomas and especially Bailey et al. Page 3 Mol Cancer Res author manuscript in PMC 2009 1 July. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript keratinocytes in the basal layer.
Equivalent concentration and distribution of cellular Their distribution of p53-F Staining were observed in the papillomas of ATM + / + and Atm � � Mice. The expression of p53-regulated gene p21 and p16 Cdk inhibitor, were also observed in the two ATM + / + and Atm � � Papillomas. As more Ma Exception of functional p53, we quantified proliferation and apoptosis. The mitotic index was � in papillomas of ATM + / + and Atm � Mice, may need during the apoptotic index, as measured by both active caspase 3 and apoptotic figures was bit on the � forth in atm � Papillomas. And Atm deficiency has no measurable effect on the levels of H2AX, p53, p21, and cell proliferation in benign tumors. It makes sense, these results with those in mice null M P19/Arf compare observed. Arf