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Northwestern Univ., Chicago, IL. offers a evaluation of the endocrine therapy of breast and prostate melanoma by means of the originators, a version for making new discoveries within the chemoprevention of melanoma, a synthesis of background and medical perform, and a advisor for development. DNLM: Breast Neoplasms--drug remedy.

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In fibroblasts, c-Myc is both necessary and sufficient for G1-S phase progression (58) and activation of conditional alleles of c-myc is followed by the activation of both cyclin D1-Cdk4 and cyclin E-Cdk2 (59–61). Rapid decreases in c-myc mRNA and protein levels are observed in response to a variety of antiestrogens in both in vivo and in vitro models (21,63,84,85), being apparent within 30 min (Fig. 9A). Therefore in addition to cyclin D1 and p21, c-Myc may be a major target molecule through which antiestrogen mediates cell-cycle control.

Cdk2 is the second major CDK acting in the G1 phase and its total cellular activity, as measured in Cdk2-immunoprecipitates, appeared to be unaffected by antiestrogen treatment between 2 and 6 h but decreased starting at 8 h (62,63). This profound inhibition of Cdk2 activity might result in pRB hypophosphorylation at late times and contribute to the sustained antiestrogen blockade of cellcycle progression. However, cyclin A/Cdk2 is the predominant form of this complex and when the subcomponent of Cdk2 associated with cyclin E was examined, a more complex picture emerged as significant decreases in kinase activity were seen prior to 12 h (Fig.

Formation of p27-cdk complexes during the human mitotic cell cycle. Cell Growth Differ 1996; 7:135–146. 57. Zhang H, Hannon GJ, Beach D. p21-containing cyclin kinases exist in both active and inactive states. Genes Dev 1994; 8:1750–1758. 58. Henriksson M, Luscher B. Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res 1996; 68:109–182. 59. Steiner P, Philipp A, Lukas J, et al. Identification of a Myc-dependent step during the formation of active G1 cyclin-cdk complexes.

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