Expression patterns of the cell-cycle inhibitor p27 and the cell-cycle promoter cyclin E in the human placenta throughout gestation: Implications forthe control of proliferation

The rapid development of the placenta necessitates a high proliferative pot ential and cell-division rate. This, coupled with a high capacity for invas ion, could confer on the placental tissue a tumour-like character. To exclu de this, tight mechanisms of control are necessary for both proliferation a nd invasiveness. Despite their importance, very little is known about the m olecular basis of these mechanisms. The present study was thus designed to investigate the molecular mechanisms implicated in the control of prolifera tion in the human placenta. We used immunohistochemistry to study the expre ssion of two cell-cycle controlling molecules with opposing effects: the ce ll-cycle inhibitor, p27, which belongs to the Kip/Cip family of CDK inhibit ors and can mediate G1 arrest, and cyclin E, a G1-cyclin esential for G1/S progression. Expression was studied throughout pregnancy in a total of 41 n ormal human placental samples. In addition, immunohistochemistry for Ki-67 was performed as a control for proliferation. The cell-cycle inhibitor p27 was expressed in the differentiated, non-dividing syncytiotrophoblast, whil e expression of cell-cycle promoter cyclin E was localized to the nuclei of the cytotrophoblast and correlated well with expression of Ki-67. No cycli n E expression was observed in the syncytiotrophoblast. In conclusion, stro ng expression of the cell-cycle inhibitor p27 and absence of expression of cyclin E in the syncytiotrophoblast might represent an important control me chanism in placental proliferation. This differentiates it from the prolife ration of malignant rumours, where p27 has been shown to be frequently down regulated while cell cycle promoters are overexpressed. (C) 1999 W. B. Saun ders Company Ltd.