We seek to identify the phases in the cell cycle during which steroid-activated estrogen and androgen receptors are normally transcriptionally active and to determine whether this cell cycle regulation of receptor activity is maintained when cancer-inducing non- steroidal agents activate the receptors. Our hypothesis is that the activities of steroid-induced ER and AR are controlled by cell cycle regulators and that cancer-inducing, non-steroidal activators bypass or alter this regulation of receptor activity giving rise to aberrant ER and AR function. Through these studies we are gaining understanding of how estrogen and androgen receptors may contribute to the onset of tumors and to the development of hormone independent growth. We have found that the activity of the androgen and estrogen receptors is indeed regulated throughout the cell cycle with no activity of the androgen receptor in the G2/Phase phase and low activity of the estrogen receptor in cells which are mainly in S phase. Furthermore, our data indicate that non-steroidal activators of the receptors may act in a cell type and promoter dependent manner as we do not detect receptor activation by growth factors in our system.

From the tissue culture dish to genetically modified mice, this volume explores the long recognized role of steroid hormones in regulating cell proliferation and differentiation. Many striking effects of steroid hormones are apparent during development and neoplasia and these topics are covered extensively. Several chapters address the pharmacological uses of steroid and related hormones, their analogs and antagonists in controlling growth of endocrine cancers. This book also highlights the complex role of cross talk between steroid hormones and signals initiated at the cell surface in the regulation of cell cycle in hormone responsive tissues.

This book covers topics that range from fundamental studies of DNA replication, chromosomal and nuclear function through growth factor control of endocrine tumor initiation and progression. The basic and translational insights gained from Hormonal Control of Cell Cycle will be of interest to those studying the biology of endocrine tumors as well as those deriving novel therapeutic approaches for these benign and malignant disorders.

The papers in this volume were presented at the Symposium on Hormones and Cancer held March 24-26, 1980, at the Worcester Foundation for Experimental Biology, Shrewsbury, MA. The meeting was organized to review recent advances in basic and clinical research work on hormone-responsive tumors of the reproductive system. The association between protracted hormone action and cancer of the reproductive system is now irrefutable. Yet we still do not know how hormones initiate and promote neoplastic transformation of their target cells. A major effort is cur rently being directed at understanding the hormonal regulation of neoplastic cells, especially those arising from the breast, uterus, pituitary gland and prostate. The symposium brought together leading experts whose research is focused on this impor tant area of human health. Although many questions remain to be answered by future studies, the material covered in this volume provides an up-to-date overview of the current status of work in this area. The subjects range from the mechanism of hormone action to the treatment of hormone-dependent tumors, and topics include estrogen, progestin, androgen and glucocorticoid action~ hormone receptors~ specific protein responses~ developmental effects of estrogens and antiestrogens~ the DES syndrome~ regu lation of the cell cycle~ therapeutic effects of antiestrogens, aromatase inhibitors, iodoestrogens, progestins on estrogen dependent tumors~ characterization of retinoid-binding sites~ and the utility of various tumor markers.

The series, Hormones in Health and Disease, was launched in 1993 to provide a scientific platform for investigators engaged in research on the biological actions of hormones and to anticipate relevance for their findings in clinical applications. The first volume of the series was dedicated to the discussion and understanding of molecular mechanisms by which steroid hormones influence target cells in normal and pathological conditions. With the diversity of information and the vast amount of literature on steroid hormone physiology, a more thorough treatment of Hormones and Cancer was identified as a timely topic. In this second volume in the series, Dr. Wayne V. Vedeckis has success fully undertaken the monumental task of editing the findings of the leading investigators in hormone and cancer research. Dr. Vedeckis brings to this project two decades of research experience in hormone action; he is actively engaged in elucidating hormone and cancer interrelations. It is a pleasure to welcome him to the series as an editor and congratulate him and all contribu tors in presenting this comprehensive treatise. The 20 chapters include discussions on contemporary topics relating control of cell division and signal transduction to the basic mechanisms of carcinogenesis by cloning patient genes, and recognizing the importance of steroid receptors in treatment protocols of various endocrine abnormalities.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together provide important insights to our understanding of hormonal cancer causation, development, and prevention; the primary objective of these Symposia. A special emphasis is placed on the two major endocrine-related cancers, that is, breast and prostate. The emerging fields of colon, lung, and pancreatic cancers in relation to hormones are examined.