title: Mechanisms of steroid hormone action and resistance in endometrial and breast cancer.
abstract: The detection of molecular alterations that lead to the development, progression, and formation of metastases in human endometrial and breast cancer may contribute to a better understanding of tumour biology as well as the development of specific preventative and therapeutic strategies. 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. Steroid hormones act directly via corresponding steroid hormone receptors or indirectly via alterations of protein kinases or (proto-)oncogenes. Oncogene amplification with concomitant overexpression of the oncoprotein seems to be specific for certain cancer types and to mediate cellular proliferation. Loss of normal tumour suppressor protein function can occur through sequential gene mutation events (somatic alteration) or through a single mutational event of a remaining normal copy, when a germline mutation is present. The second event is usually chromosome 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 therapeutic interventions.
authors.affiliation: Department of Gynecology & Obstetrics, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: M W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: D
authors.initials: D
authors.lastname: Niederacher
authors.forename: H G
authors.initials: HG
authors.lastname: Bender
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics; D016889:Endometrial Neoplasms / Q000209:etiology* / Q000235:genetics; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006801:Humans
chemical_list: D004967:Estrogens