MECHANISMS OF STEROID-HORMONE ACTION AND RESISTANCE IN ENDOMETRIAL AND BREAST-CANCER

The detection of molecular alterations that lead to the development, p rogression, and formation of metastases in human endometrial and breas t cancer may contribute to a better understanding of tumour biology as well as the development of specific preventative and therapeutic stra tegies. Endometrial and breast cancers both emerge during a multistep process. Cytogenetic and molecular genetic analysis of cancer samples suggest that tumour development involves: (1) alterations of hormonal interactions, and (2) accumulation of various genetic alterations. Ste roid hormones act directly via corresponding steroid hormone receptors or indirectly via alterations of protein kinases or (proto-) oncogene s. Oncogene amplification with concomitant overexpression of the oncop rotein seems to be specific for certain cancer types and to mediate ce llular proliferation. Loss of normal tumour suppressor protein functio n can occur through sequential gene mutation events (somatic alteratio n) or through a single mutational event of a remaining normal copy, wh en a germline mutation is present. The second event is usually chromos ome loss, mitotic recombination, or partial chromosome deletion. These alterations of interactions or different regulatory cellular pathways may lead to primary or secondary hormonal resistance during therapeut ic interventions. (C) 1998 Rapid Science Ltd.