title: Tyrosine phosphorylation of Grb2: role in prolactin/epidermal growth factor cross talk in mammary epithelial cell growth and differentiation.
abstract: Characterizing mechanisms regulating mammary cell growth and differentiation is vital, as they may contribute to breast carcinogenesis. Here, we examine a cross talk mechanism(s) downstream of prolactin (PRL), a primary differentiation hormone, and epidermal growth factor (EGF), an important proliferative factor, in mammary epithelial cell growth and differentiation. Our data indicate that EGF exerts inhibitory effects on PRL-induced cellular differentiation by interfering with Stat5a-mediated gene expression independent of the PRL-proximal signaling cascade. Additionally, our data show that PRL is a potent inhibitor of EGF-induced cell proliferation. We identify tyrosine phosphorylation of the growth factor receptor-bound protein 2 (Grb2) as a critical mechanism by which PRL antagonizes EGF-induced cell proliferation by attenuating the activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. Together, our results define a novel negative cross-regulation between PRL and EGF involving the Jak2/Stat5a and Ras/MAPK pathways through tyrosine phosphorylation of Grb2.
authors.affiliation: Hormones and Cancer Research Unit, Department of Medicine, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Haines
authors.forename: Parham
authors.initials: P
authors.lastname: Minoo
authors.forename: Zhenqian
authors.initials: Z
authors.lastname: Feng
authors.forename: Nazila
authors.initials: N
authors.lastname: Resalatpanah
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Nie
authors.forename: Manuela
authors.initials: M
authors.lastname: Campiglio
authors.forename: Laura
authors.initials: L
authors.lastname: Alvarez
authors.forename: Eftihia
authors.initials: E
authors.lastname: Cocolakis
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ridha
authors.forename: Mauricio
authors.initials: M
authors.lastname: Di Fulvio
authors.forename: Julian
authors.initials: J
authors.lastname: Gomez-Cambronero
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lebrun
authors.forename: Suhad
authors.initials: S
authors.lastname: Ali
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases; D005260:Female; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D042361:Mammary Glands, Human / Q000166:cytology* / Q000502:physiology; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051380:GRB2 Adaptor Protein; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; D004815:Epidermal Growth Factor; D011388:Prolactin; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins