CHRISTOPHER KEMP

..This indicates that selection for p53 mutations is a direct result of signaling from the initiating oncogenic lesion, Hras, acting through p19(Arf)...

..This hypersensitivity of SCID (severe combined immunodeficient) cells to TPA indicates that the resistance to skin tumor formation in scid/scid mice is due to loss of initiated cells through TPA-induced cell killing...

..This indicates that tumor cells have an inherent reduced capacity to buffer against perturbations. Reduced buffering may play an important role in both tumor evolution and therapy response and may be a hallmark of cancer cells...

..This variation provides one explanation for the tissue specificity of tumor suppression by p53. It also indicates that the role of apoptosis in the response of tumors to therapy varies significantly among tumor types...

..These results indicate that reduction of p27 cooperates with mutations in Apc but not in Smad3 during GI tumorigenesis. Thus, tumor suppression by p27 is contingent on the specific oncogenic pathway that drives tumor development...

..This indicates that marked differences in DNA damage signaling pathways exist between tissues, which could explain some of the tissue-specific phenotypes, especially tumor suppression, associated with Atm deficiency...

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..Although p21 is functionally similar to both p53 and p27, it plays a lesser role in tumor suppression. These results further highlight the highly cooperative nature of p27 and its central role in tumor suppression...

..This study demonstrates that tissues dependent on Cx32 tumor suppression, such as the liver and lung, exhibit altered tumorigenesis and tumor biology (MAPK pathway activation) related to p27 status...

..This study shows that while not a significant inhibitor of Wnt-1-driven breast cancer, p27 inhibits gastric tumors, whose latency is modulated by sex steroids...

..We further identify, by tandem mass spectrometry, some of the peptides that were consistently elevated in cancer mice compared with their control littermates...

..In conclusion, in these models of oncogene- or DNA damage-induced tumors, p53 retains tumor suppressor activity in the absence of Atm...

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..The second is by transient inhibition of cell cycle progression following genotoxic insult, thereby minimizing chromosome damage and fixation of mutations...

..Incorporating these new findings into existing models of the clonal evolution will be a challenge for the future...

..Thus, phosphorylation of p27 on Ser10 is an important event in the regulation of the tumor suppressor function of p27...

..Furthermore, the approach can be extended to find biomarkers relevant to human disease...

..005) and dermis (P < 0.01). CONCLUSION: OCT is a viable tool for assessing the earliest stages of carcinogenesis and has potential for early detection of neoplasia in skin, as well as in epithelial linings of other organs...

..This shows that there are two separate, but equally effective, apoptotic responses to DNA damage: one is p53 dependent and the other, engaged in the absence of DNA-PK, does not require p53...

..Hence, treatment of cancer patients with agonists of the apoptosis-inducing receptors for TRAIL may prove useful in reducing the incidence of metastasis...

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..These findings do not support a critical role for EGF or its receptor in chemotherapy-induced intestinal injury...

..We present the overall design of this resource and its potential use by the research community for biomarker discovery...

..Understanding the functional interaction of the P13 Ks, in regulating p53, apoptosis, development and carcinogenesis at the level of the whole animal is a necessary link to apply knowledge gained from cell culture models to the clinic. ..

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..These experiments will reveal the molecular and cellular basis for the poor clinical outcome associated with p27 deficient tumors. This knowledge can then be applied to improve treatment design and regimen in the clinical setting. ..