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

The rapid development of the placenta necessitates a high proliferative potential and cell-division rate. This, coupled with a high capacity for invasion, could confer on the placental tissue a tumour-like character. To exclude this, tight mechanisms of control are necessary for both proliferation and invasiveness. Despite their importance, very little is known about the molecular basis of these mechanisms. The present study was thus designed to investigate the molecular mechanisms implicated in the control of proliferation in the human placenta. We used immunohistochemistry to study the expression of two cell-cycle controlling molecules with opposing effects: the cell-cycle inhibitor, p27, which belongs to the Kip/Cip family of CDK inhibitors 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 normal 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, while expression of cell-cycle promoter cyclin E was localized to the nuclei of the cytotrophoblast and correlated well with expression of Ki-67. No cyclin E expression was observed in the syncytiotrophoblast. In conclusion, strong expression of the cell-cycle inhibitor p27 and absence of expression of cyclin E in the syncytiotrophoblast might represent an important control mechanism in placental proliferation. This differentiates it from the proliferation of malignant tumours, where p27 has been shown to be frequently downregulated while cell cycle promoters are overexpressed. Copyright 1999 W.B. Saunders Company Ltd.