Expression Of CDK₂,CDK₄,C-JUN In Premalignant And Malignant Lesions Of Hamster Cheek Pouch

Deregulated cellular cycle is one of the important carinogenesis mechanisms. Cyclin dependent kinases(CDKs) is a protein that is encoded by cell division cycle gene(cdc gene).It participates in the regulation of cellular cycle directly. Many researches indicated that the activities of CDK2,CDK4 in cellular cycle are associated with the occurrence and development of many malignant tumours. Currently, CDKs was found to be a super family, including 7 subunits named CDK1-7 respectively. CDKs gene lies in NO.13 domain of NO.12 chromosome, and CDKs is 35-40KD in size ,with more than 40% the same sequence. The typical CDK catalytic subunit contains a 300 amino acid catalytic core that is completely inactive when monomeric and unphosphorylated. The activity of CDKs is controlled by four highy conserved biochemical mechanisms: 1).CDK activation by cyclin binding. Homology among cyclins is often limited to a relatively conserved domain of about 100 amino acids, the cyclin box, which is responsible for CDK binding and activation. 2).CDK activation by phosphorylation. In addition to cyclin binding, complete CDK activation requires phosphorylation at a conserved threonine residue(Thr 160 in CDK2). Phosphorylation may affect the cyclin binding site, as it enhances the binding of some CDK-cyclin pairs, conversely, cyclin binding may enhance phosphorylation.During the normal vertebrate cell cycle,phosphorylation of Thr 160/161 tends to rise and fall in parallel with cyclin binding. 3).CDK inhibition by phosphorylation. There are many ways to inactivate a CDK-cyclin complex. Two of the most obvious are to remove the cyclin or dephosphorylate Thr160/161. CDK-cyclin complexes can also be inhibited by phosphorylation at two sites near the amino terminus which is Thr14 and Tyr15 in human CDC2 and CDK2. 4). CDK inhibition by inhibitory subunits(CKIs) CKI, that bind and inactivate CDK-cyclin complexes, as inhibit the activity of CDK. At G1/S checkpoint among the cellular circle phases (G1→S→G2→M), CDK2, and CDK4 play a positive role in modulation. At G1 phase, CDK4 activated by the combination with cyclinD, promotes cellular circle from G1 phase to S phase. At the late G1 phase, CDK2 combined with cyclinE, accelerates cellular circle from G1 phase to S phase. CyclinD1-CDK4 and cyclinE-CDK2 have an effect on retinoblastoma(Rb) protein phosphorylation, and consequently, Rb can't inhibit transcription factor E2F that can start DNA synthesis, thus cellular cycle is accelerated from G1 phrase to S phrase. Protein product of oncogene participates in the regulation of cellular cycle in various ways. Proto-oncegene mutant and abnormal transcription lead to malignant tumours. C-jun is an eukyotic oncogene and is an early transcription active factor with the following characters:1).When cells are stimulated from extracellular signals, they can be quickly induced into transcription and expression, whose protein regulates transcription and expression of other genes. 2). Half-life of c-jun mRNA and its encoded protein is short. 3).C-jun has the structure of leucine-zipper, which may form homodimer or heterodimer with c-fos, and is able to bind specific DNA sequences. Currently, Fos/jun protein is believed to be a "transmission station" of different signal transference in transcription level and has the ability of interacting with various transcription factors and nucleo-receptor and participating in the regulation of cell circle phases.In this study, We induced premalignant and Malignant Lesions of Hamster Cheek Pouch by 7,12-dimethylbenhracence. We examined the expression of CDK2,CDK4,c-jun in 23 cases of normal oral mucosa, 22 cases of oral epithelial hyperplasia, 22 cases of oral epithelial dysplasia, and 29 cases of squamous cell carcinoma(OSCC) by means of immunohistochemical SABC method. There was a gradual increase in positive signal intensity and in positive cells in the expression of CDK2 and CDK4 from normal mucosa, hyperplasia, abnormal hyperplasia to OSCC. There is a remarkable contrast in the expression of CD...