title: ErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy.
abstract: Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies.
authors.affiliation: Laboratory of Molecular Mechanisms of CarcinogenesisInstituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina patriciaelizalde@ibyme.conicet.gov.ar.
authors.forename: Patricia V
authors.initials: PV
authors.lastname: Elizalde
authors.affiliation: Laboratory of Molecular Mechanisms of CarcinogenesisInstituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina.
authors.forename: Rosalía I
authors.initials: RI
authors.lastname: Cordo Russo
authors.affiliation: Laboratory of Molecular Mechanisms of CarcinogenesisInstituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Chervo
authors.affiliation: Laboratory of Molecular Mechanisms of CarcinogenesisInstituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina.
authors.forename: Roxana
authors.initials: R
authors.lastname: Schillaci
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases
keywords: ErbB-2 transcriptional activity; breast cancer growth; metastasis; nuclear ErbB-2; response to anti-ErbB-2 therapies