Manuscript J recombination, w While p53-null mouse lymphoma arose independently Ngig of the VJ recombination. ATM has recently featured in the previous year break repair was w While involved in antigen KX2-391 receptor rearrangement, and this function could play an r In the L Lymphoma Research minimizing oncogenic translocations 6th In line with this idea, translocations involving the antigen receptors are frequently seen in lymphoid tumors from two patients at 45 atm and mouse 2; 51st In summary, the requirement of ATM in p53 regulation varies in response to DNA-Sch Ending from tissue to tissue, the at least partially capable of Ren r explained The tissue-specific tumor suppressor ATM. Studied in tumor models, makes the loss of Atm Ph Nokopie the loss of p53, a significant p53 tumor suppressor activity obtained t remains in the absence of Atm.
This highlights that there are multiple and in some F Cases, redundant signals that can activate p53 in tumor suppression k. In case of skin tumors, Ras-entered Born, seems to be a Arf Most important Elesclomol in the regulation of p53 and ATM play tumor progression. Identify the rate-limiting steps in tumor progression in different tumor models and in various tumor remains Etiology is an important goal in cancer research. In another picture that fully understand the nature of the selective pressure to drive tumor progression is a necessary step in the development of effective treatment methods to mechanistic basis. Materials and methods F1 mouse NIH / FVB, mice, 129 TRp53F2-10 / + M 23 crossed to K14-Cre N1 NIH/C57 mice47 and offspring crossed to Mice With experimental genotypes and Trp53F2-10/F2-10 generate Trp53F2-10 / F2-10, K14-Cre.
PCR analysis best Firmed that p53 was suppressed in the epidermis, but not the liver, spleen or thymus. The backs of the 8-week-old WT function of p53 and p53 0 Mice were shaved and treated with a functional single application of DMBA and a week later Ter w twice Weekly applications of TPA for 15 weeks. The number and size E of papillomas on each mouse was w Recorded weekly. Mice were get Tet, when dying, or one to three weeks after the detection of cancer. All major organs were examined and tumors were used for DNA extraction and / or processed frozen in formalin and found Rbt with H & E for histological examination. For the study of skin tumors ATM Atm knockout allele was backcrossed 13 times its impact on free NIH / Ola.
Experimental mice M All three genotypes were then Atm NIH / Ola Atm �� generated shipowner. atm , ATM + / And ATM + / + M were Mice treated as above. For spontaneous and radiation-induced tumor models, 129/SvEv Atm + / 3 and C57BL6 p53 + / 13 Mice were crossed to Versuchsm ben Mice CONFIRMS combination of ATM and p53 genotypes generate. One group was left untreated and additionally irradiated one USEFUL cohort at two days old. Experimental Mice get Tet and subjected to autopsy, the symptoms of the tumor burden. Histological sections of normal tissue or tumor were removed and either frozen or snap set for four hours in normal buffered formalin and then processed to paraffin. 4 m sections were cut μ, deparaffinized and stained for H & E, p53, p21, p16, caspase-3, phospho-histone H2A.
X and phospho-Chk2. P19/Arf apillomas stained for p53 were from a previous study 24th The F Staining for all antique Body was carried out using a three-step technique streptavidin. Sections were rehydrated and W Rmer��ckgewinnung of antigen using a 10 mM citrate buffer, then with primary rabbit Found from Ren. To F Staining with primary Ren Antique been Body, the sections with a biotin-conjugated secondary Al Ren Bailey et al found Rbt. Page 6 Mol Cancer Res author manuscript in PMC 2009 1 July. Manuscript NIH-PA writer writer writer Manuscript NIH-PA Manuscri NIH-PA