title: Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells.
abstract: The pituitary hormone prolactin (PRL) plays an important role in mammary gland development. It was also suggested to contribute to breast cancer progression. In vivo data strongly supported a crucial role of PRL in promoting tumour growth; however, PRL demonstrated only a weak, if any, pro-proliferative effect on cancer cells in vitro. Several recent studies indicated that PRL action in vivo may be influenced by the hormonal milieu, e.g. other growth factors such as 17beta-oestradiol (E(2)). Here, we explored the potential interplay between PRL and E(2) in regulation of gene expression and cell growth. PRL alone induced either a weak or no proliferative response of T47D and BT-483 cells respectively, while it drastically enhanced cell proliferation in E(2)-stimulated cultures. Affymetrix microarray analysis revealed 12 genes to be regulated by E(2), while 57 genes were regulated by PRL in T47D cells. Most of the PRL-regulated genes (42/57) were not previously described as PRL target genes, e.g. WT1 and IER3. One hundred and five genes were found to be regulated upon PRL/E(2) co-treatment: highest up-regulation was found for EGR3, RUNX2, EGR1, MAFF, GLIPR1, IER3, SOCS3, WT1 and AREG. PRL and E(2) synergised to regulate EGR3, while multiple genes were regulated additively. These data show a novel interplay between PRL and E(2) to modulate gene regulation in breast cancer cells.
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, Novo Nordisk Park G8.1.55, Maaloev, Denmark.
authors.forename: Louise Maymann
authors.initials: LM
authors.lastname: Rasmussen
authors.forename: Klaus Stensgaard
authors.initials: KS
authors.lastname: Frederiksen
authors.forename: Nanni
authors.initials: N
authors.lastname: Din
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Galsgaard
authors.forename: Leif
authors.initials: L
authors.lastname: Christensen
authors.forename: Martin Werner
authors.initials: MW
authors.lastname: Berchtold
authors.forename: Svetlana
authors.initials: S
authors.lastname: Panina
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D004357:Drug Synergism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011981:Receptors, Prolactin; D011388:Prolactin