title: Growth factor messenger RNA expression by human breast fibroblasts from benign and malignant lesions.
abstract: Breast tumors are a complex mix of epithelial, stromal, and vascular elements. We examined primary cultures of breast fibroblasts derived from benign and malignant lesions for expression of various growth factors. All fibroblast cultures, regardless of whether they were derived from benign or malignant lesions, expressed platelet-derived growth factor A chain, basic fibroblast growth factor, fibroblast growth factor 5, and transforming growth factor beta 1 mRNA. None expressed platelet-derived growth factor B chain or transforming growth factor alpha mRNA. However, examination of mRNA expression for the insulin-like growth factors revealed that 7 of 8 fibroblasts derived from benign lesions expressed insulin-like growth factor I (IGF-I) mRNA, while only 1 of 9 fibroblasts derived from malignancies expressed IGF-I mRNA. The opposite picture was seen for insulin-like growth factor II (IGF-II) mRNA expression, in which 1 of 9 benign-derived fibroblasts expressed IGF-II mRNA, while 5 of 9 malignant-derived fibroblasts expressed IGF-II. This correlated with previous in situ hybridization data, which showed IGF-I mRNA expression confined to the stroma of benign breast tissue. PDGF treatment of tumor fibroblasts resulted in a 3-fold increase in IGF-II mRNA. Thus there was an apparent dichotomy between IGF-I mRNA expression in the majority of fibroblasts derived from benign lesions and IGF-II mRNA expression in the majority of tumor-derived fibroblasts. Since the insulin-like growth factors are potent mitogens for breast tumor epithelial cells, this further supports the notion of a paracrine growth-promoting role for the insulin-like growth factors in breast lesions and suggests that IGF-II may be the more important growth promoter in malignant lesions.
authors.affiliation: Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007.
authors.forename: K J
authors.initials: KJ
authors.lastname: Cullen
authors.forename: H S
authors.initials: HS
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Hill
authors.forename: N
authors.initials: N
authors.lastname: Rosen
authors.forename: M E
authors.initials: ME
authors.lastname: Lippman
mesh_terms: D001941:Breast Diseases / Q000235:genetics* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012260:Ribonucleases / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C496449:FGF5 protein, human; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012260:Ribonucleases