title: Autocrine stimulation of human mammary carcinoma cell proliferation by human growth hormone.
abstract: Here we have investigated the role of autocrine production of human growth hormone (hGH) in the proliferation of mammary carcinoma cells (MCF-7) in vitro. MCF-7 cells were stably transfected with an expression plasmid encoding the hGH gene, and these cells (designated MCF-hGH) synthesized hGH in the cell and secreted hGH to the medium. For control purposes, a MCF cell line was generated (MCF-MUT) in which the start codon of the hGH gene was disabled, and these cells transcribed the hGH gene without translation to hGH protein. The MCF-hGH cell number increased at a rate significantly greater than that of MCF-MUT under serum-free conditions. Autocrine hGH also synergized with 10% serum and insulin-like growth factor-1 but not 17-beta-estradiol to increase cell number. The increased proliferation of MCF-hGH cells in both serum-free and serum-containing media could be completely abrogated by the use of the nonreceptor dimerizing hGH antagonist, hGH-G120R. Increased mitogenesis as a consequence of autocrine production of hGH was prevented by inhibition of either the p38 MAPK or p42/44 MAPK pathways. MCF-hGH cells also possessed a higher level of STAT5 (but not STATs 1 and 3) mediated transcriptional activation in both serum-free and serum-containing conditions than MCF-MUT cells. Thus we conclude that hGH can act in an autocrine/paracrine manner in human mammary carcinoma cells to promote cell proliferation and transcriptional activation.
authors.affiliation: National University Hospital, National University of Singapore, 10 Kent Ridge Crescent, Singapore, 119260, Republic of Singapore.
authors.forename: K K
authors.initials: KK
authors.lastname: Kaulsay
authors.forename: H C
authors.initials: HC
authors.lastname: Mertani
authors.forename: J
authors.initials: J
authors.lastname: Törnell
authors.forename: G
authors.initials: G
authors.lastname: Morel
authors.forename: K O
authors.initials: KO
authors.lastname: Lee
authors.forename: P E
authors.initials: PE
authors.lastname: Lobie
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D019898:Autocrine Communication; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000473:pathology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008894:Milk Proteins; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004268:DNA-Binding Proteins; C093172:G120R protein, human; D006727:Hormone Antagonists; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases