title: Cracking the estrogen receptor's posttranslational code in breast tumors.
abstract: Estrogen signaling pathways, because of their central role in regulating the growth and survival of breast tumor cells, have been identified as suitable and efficient targets for cancer therapies. Agents blocking estrogen activity are already widely used clinically, and many new molecules have entered clinical trials, but intrinsic or acquired resistance to treatment limits their efficacy. The basic molecular studies underlying estrogen signaling have defined the critical role of estrogen receptors (ER) in many aspects of breast tumorigenesis. However, important knowledge gaps remain about the role of posttranslational modifications (PTM) of ER in initiation and progression of breast carcinogenesis. Whereas major attention has been focused on the phosphorylation of ER, many other PTM (such as acetylation, ubiquitination, sumoylation, methylation, and palmitoylation) have been identified as events modifying ER expression and stability, subcellular localization, and sensitivity to hormonal response. This article will provide an overview of the current and emerging knowledge on ER PTM, with a particular focus on their deregulation in breast cancer. We also discuss their clinical relevance and the functional relationship between PTM. A thorough understanding of the complete picture of these modifications in ER carcinogenesis might not only open new avenues for identifying new markers for prognosis or prediction of response to endocrine therapy but also could promote the development of novel therapeutic strategies.
authors.affiliation: Université de Lyon, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Bâtiment Cheney D, 28 rue Laennec, 69373 Lyon Cedex 08, France. leroman@lyon.fnclcc.fr
authors.forename: Muriel
authors.initials: M
authors.lastname: Le Romancer
authors.forename: Coralie
authors.initials: C
authors.lastname: Poulard
authors.forename: Pascale
authors.initials: P
authors.lastname: Cohen
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Sentis
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
authors.forename: Laura
authors.initials: L
authors.lastname: Corbo
mesh_terms: D000107:Acetylation; D000818:Animals; D018931:Antineoplastic Agents, Hormonal; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000235:genetics / Q000502:physiology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D008745:Methylation; D009154:Mutation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D011960:Receptors, Estrogen / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen