title: Heregulin regulation of autocrine motility factor expression in human tumor cells.
abstract: The exposure of cells to growth factors has been shown to induce cytoskeleton reorganization, leading to stimulation of cell motility and invasion. Heregulin beta1 (HRG), a combinatorial ligand for human epidermal growth factor receptor 3 and human epidermal growth factor receptor 4 receptors, is a regulatory secretory polypeptide with a distinctive function in promoting motility and invasiveness of breast cancer cells. In addition to HRG, motility and invasiveness of tumor cells may also involve up-regulation of expression and function of the autocrine motility factor (AMF). Here we explored the possible involvement of AMF in the motility-promoting action of HRG in the MCF-7 breast cancer cell model system. We report that HRG increases the expression of AMF mRNA by 3-8-fold in an actinomycin D-sensitive manner and does not require de novo protein synthesis. The HRG-induced stimulation of AMF expression was inhibited by specific inhibitors of p42/44MAPK and p38MAPK kinases, but not by an inhibitor of the phosphatidylinositol 3'-kinase pathway. Other HRG-responsive human cell lines demonstrated that HRG does indeed significantly up-regulate AMF expression. Furthermore, HRG-stimulated increased motility was partially suppressed by inclusion of an anti-AMF antibody to breast cancer cells, suggesting that a HRG-mediated increase in cell motility may be mediated, at least in part, via induction of AMF. The present study is the first demonstration of AMF regulation by a growth factor and suggests a potential role for AMF in HRG regulation of breast cancer cell motility and a novel function of HRG as a regulator of motility factor expression.
authors.affiliation: Cell Growth Regulation Laboratory, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Talukder
authors.forename: L
authors.initials: L
authors.lastname: Adam
authors.forename: A
authors.initials: A
authors.lastname: Raz
authors.forename: R
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000906:Antibodies; D001943:Breast Neoplasms; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms; D015179:Colorectal Neoplasms; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005956:Glucose-6-Phosphate Isomerase / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020890:Neuregulin-1 / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D000906:Antibodies; D020890:Neuregulin-1; D010446:Peptide Fragments; D012333:RNA, Messenger; C087230:heregulin beta1; D005956:Glucose-6-Phosphate Isomerase