title: Membrane-initiated steroid action in breast and prostate cancer.
abstract: The mode of action of steroid hormones has been extended in recent years. In addition to their classical nuclear action (acting as transcription factors), they can also regulate cell-signaling phosphorylation cascades and exert actions that are initiated at the membrane and which, in most cases, are rapid. Even though research in this field was intensified during the last decade the nature of the up-stream receptor targets that mediates these rapid non-genomic actions remains to be better established. However, it became obvious that steroid signaling is not uniform, with a variety of modes of rapid action being described. There are several studies speculating a classical steroid receptor involvement in the rapid effects of steroids, localized at the cytoplasmic membrane and mediating effects directly or indirectly, via interactions with specific membrane structures (estrogen receptor (ER) isoforms have been shown to localize in caveolae) and/or other membrane receptors (like growth factor receptor). In addition, there are reports that suggest the existence of a distinct receptor, associated to the plasma membrane, being different from the classical, intracellular one. Non-genomic/extranuclear actions of steroids have been described in a number of different normal or cancer tissues independently of the presence of classical nuclear steroid receptors. In the present work, we review briefly the identification and signaling events of membrane-initiated steroid (androgen and estrogen) action in breast and prostate cancer cell lines and clinical specimens. Furthermore, we discuss the interaction of cytokine/growth factor receptors with membrane-acting steroids and their potential clinical implications.
authors.affiliation: Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion, Greece.
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D011372:Progestins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms; D011960:Receptors, Estrogen / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism*
chemical_list: D016207:Cytokines; D011372:Progestins; D020033:Protein Isoforms; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D013256:Steroids