title: Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer.
abstract: Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine-Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid-sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer. The data are complemented by an analysis of the expression levels of each selected Nuclear-Receptor in the PAM50 breast-cancer groups, following re-elaboration of the data publicly available. The major aim is to support the idea that some of the Nuclear-Receptors represent largely unexploited therapeutic-targets in breast-cancer treatment/chemo-prevention. On the basis of our analysis, we conclude that the Lipid-Sensors, NR1C3, NR1H2 and NR1H3 are likely to be onco-suppressors in breast-cancer. The Enigmatic-Orphans, NR1F1 NR2A1 and NR3B3 as well as the Orphan-Receptors, NR0B1, NR0B2, NR1D1, NR2F1, NR2F2 and NR4A3 exert a similar action. These Nuclear-Receptors represent candidates for the development of therapeutic strategies aimed at increasing their expression or activating them in tumor cells. The group of Nuclear-Receptors endowed with potential oncogenic properties consists of the Lipid-Sensors, NR1C2 and NR1I2, the Enigmatic-Orphans, NR1F3, NR3B1 and NR5A2, as well as the Orphan-Receptors, NR2E1, NR2E3 and NR6A1. These oncogenic Nuclear-Receptors should be targeted with selective antagonists, reverse-agonists or agents/strategies capable of reducing their expression in breast-cancer cells.
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Garattini
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Bolis
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gianni'
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Paroni
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Fratelli
authors.affiliation: Laboratory of Molecular Biology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Mineko
authors.initials: M
authors.lastname: Terao
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000628:therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D010802:Phylogeny; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D014158:Transcription, Genetic; D016896:Treatment Outcome
chemical_list: D008024:Ligands; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057093:Orphan Nuclear Receptors; C539738:RORA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid
keywords: breast cancer; chemo-prevention; drug targets; nuclear receptors; treatment