title: HER3 is required for the maintenance of neuregulin-dependent and -independent attributes of malignant progression in prostate cancer cells.
abstract: HER3 (ERBB3) is a catalytically inactive pseudokinase of the HER receptor tyrosine kinase family, frequently overexpressed in prostate and other cancers. Aberrant expression and mutations of 2 other members of the family, EGFR and HER2, are key carcinogenic events in several types of tumors, and both are well- validated therapeutic targets. In this study, we show that HER3 is required to maintain the motile and invasive phenotypes of prostate (DU-145) and breast (MCF-7) cancer cells in response to the HER3 ligand neuregulin-1 (NRG-1), epidermal growth factor (EGF) and fetal bovine serum. Although MCF-7 breast cancer cells appeared to require HER3 as part of an autocrine response induced by EGF and FBS, the response of DU-145 prostate cancer cells to these stimuli, while requiring HER3, did not appear to involve autocrine stimulation of the receptor. DU-145 cells required the expression of HER3 for efficient clonogenicity in vitro in standard growth medium and for tumorigenicity in immunodeficient mice. These observations suggest that prostate cancer cells derived from tumors that overexpress HER3 are dependent on its expression for the maintenance of major attributes of neoplastic aggressiveness, with or without cognate ligand stimulation.
authors.affiliation: Department of Molecular and Cell Biology, Barcelona Molecular Biology Institute, CSIC, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Soler
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancini
authors.forename: Oscar
authors.initials: O
authors.lastname: Meca-Cortés
authors.forename: Lourdes
authors.initials: L
authors.lastname: Sánchez-Cid
authors.forename: Nuria
authors.initials: N
authors.lastname: Rubio
authors.forename: Sonia
authors.initials: S
authors.lastname: López-Fernández
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Blanco
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Fernández
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Thomson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: D020890:Neuregulin-1; D012333:RNA, Messenger; D020893:Receptor, ErbB-3