The Expression of G 1S Cell Cycle Inhibitors in Normal Placenta and Gestational Trophoblastic Diseases

tumor cells endure damage to the genes that directly regulate their cell cycles. In the cell cycle, the period from the late G1 to the S phase is the most important period for cell proliferation. This phase functions as an intricate system of safeguards and checkpoints that are mainly mediated by p53 and pRb, and this facilitates quality control by constantly surveying the ordered progression through the cell division cycle. Phosphorylation of pRb occurs via a molecular on/off switch at the G1/S checkpoint and this is induced by cyclin D1-cyclin-dependent kinase (cdk) 4 or the cdk6 complex, and the cyclin E-cdk2 complex. A number of cdk inhibitors (CKIs) that bind with specific cdks prevent unrestrained proliferation. The two CKI subtypes include the INK (inhibitor of kinase) family, which includes p16 (INK4a), p15 (INK4b), p18 (INK4c) and p19 (INK4d), and the cdkinteracting protein/kinase-inhibitory protein (CIP/KIP) family, which includes p21 (WAF1/CIP1), p27 (KIP1) and p57 (KIP2). It has been demonstrated that the p21 expression is regulated by wild-type p53. However, the p53-independent pathways that result in p21 induction may represent an alternative pathway to control cell growth. The expression of the major G1/S inhibitors, including p53, pRb, p16, p21 and p27, in the placenta is relatively unknown. In addition, there have been no comprehensive studies regard-

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