p12CDK2-AP1 in Cell Cycle Control & Oral Carcinogenesis

产品说明：临床相关性、体外和体内研究强烈表明，细胞周期进程的失调可导致包括癌症在内的增殖性疾病。促有丝分裂刺激和负生长调节剂调节细胞增殖，而抗增殖信号则用于门控对有丝分裂原的增殖反应。这些研究的长期目标是深入了解p12 cDk 2-ap 1在细胞周期调节以及正常和口腔癌发展中的作用，p12 cDk 2-ap 1已知是一种生长抑制因子。了解其通过与细胞周期蛋白依赖性激酶-2（CDK 2）的关联在细胞周期控制中的作用机制可能在癌症的预防和治疗中具有临床应用。如形态学、倍增时间和密度依赖性生长研究所示，体外口腔癌细胞中p12（c1）raAel的再表达与转化表型的逆转有关。最近的数据进一步将p12 cDm-Ael与TGF-β 1抗增殖途径联系起来，作为TGF-β 1介导的低磷酸化中的CDK 2负调节剂。本申请的目的包括表征p12 CDK 2-API作为CDK 2活性的负调节剂的体内作用，并确定这种相互作用如何参与TGF-β 1-抗增殖途径。未来临床应用的长期目标是，具体目的包括1）鉴定负责TGF-β 1诱导p12基因的顺式和反式元件，2）检测p12 CDK 2-API的体内作用和抗增殖作用的分子细节，和3）通过检测p12 cDrdAm、CDK 2、TGF-β 1信号传导组分和pRB在正常和癌症口腔上皮中的体内表达谱来验证体外结果。

DESCRIPTION: Clinical correlation, in vitro and in vivo studies strongly suggest that deregulation of cell-cycle progression can result in proliferative disorders including cancer. Mitogenic stimuli and negative growth regulators regulate cellular proliferation, while anti-proliferative signals serve to gate the proliferative response to mitogens. The long-term goal of these studies is to gain insight into the role of p12 cDk2-ap1, known to be a growth suppressor, in cell-cycle regulation, and normal and oral cancer development. Understanding its mechanism of action in cell-cycle control via its association with cyclin-dependent kinases- 2 (CDK2) may have clinical applications in the prevention and treatment of cancer. Re-expression of p12 c1) raAel in oral cancer cells in vitro is associated with reversion of transformation phenotypes, as indicated by morphological, doubling time and density-dependent growth studies. Recent data further tie p12 cDm-Ael to the TGF-beta1 anti-proliferative pathway as a CDK2 negative regulator in TGF- [31-mediated hypophosphorylation. The Aims of this application include characterizing the in vivo role of p12 CDK2-API as a negative regulator of CDK2 activities and determining how this interaction is involved in the TGF-beta1-antiproliferative pathways With the long-range objective of future clinical applications, Specific Aims include 1) identification of the cis and trans elements responsible for the TGF-beta1 induction of the p12 gene, 2) examination of the molecular details of an in vivo role for p12CDK2-API and the anti-proliferative effect and 3) validation of in vitro results by examining the expression profiles of p12 cDrdAm, CDK2, TGF-beta1 signaling components and pRB in normal and cancer oral epithelia in vivo.