Epidermal growth factor and hepatocyte growth factor receptors collaborate to induce multiple biological responses in bovine mammary epithelial cells

• Published in: Journal of dairy science 2009-08, Vol.92 (8), p.3667-3675
• Main Authors: Accornero, P, Martignani, E, Miretti, S, Starvaggi Cucuzza, L, Baratta, M
• Format: Article
• Language: English
• Subjects: Animal productions; Animals; biochemical pathways; Biological and medical sciences; bovine mammary cell; Cattle - metabolism; Cattle - physiology; cell differentiation; Cell Line; cell lines; cell motility; Cell Movement - drug effects; cell proliferation; Cell Proliferation - drug effects; cooperation; cytokines; dairy cows; epidermal growth factor; Epidermal Growth Factor - pharmacology; epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; extracellular matrix; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Food industries; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression Regulation - drug effects; hepatocyte growth factor; Hepatocyte Growth Factor - pharmacology; in vitro studies; mammary development; mammary glands; Mammary Glands, Animal - cytology; mechanism of action; mesenchymal-epithelial transition factor (MET); Milk and cheese industries. Ice creams; protein synthesis; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-met - metabolism; Receptor, Epidermal Growth Factor - metabolism; receptors; RNA, Messenger - metabolism; signal transduction; Signal Transduction - drug effects; Terrestrial animal productions; Vertebrates
• ISSN: 0022-0302; 1525-3198
• DOI: 10.3168/jds.2008-1835

The aim of this work was to explore whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) could increase the biological responses of a mammary epithelial cell line of bovine origin when added simultaneously. We also investigated a possible molecular mechanism underlying this cooperation. The development of mammary gland requires several circulating and locally produced hormones. Hepatocyte growth factor and its tyrosine kinase receptor, mesenchymal-epithelial transition factor (MET), are expressed and temporally regulated during mammary development and differentiation. Epidermal growth factor receptor and its ligands have also been implicated in the growth and morphogenesis of the mammary epithelium. Both EGF and HGF seem to exert a morphogenic program in this tissue; therefore, we hypothesized that these cytokines could act cooperatively in bovine mammary epithelial cells. We have already shown that the bovine BME-UV cell line, a nontumorigenic mammary epithelial line, expresses both MET and EGF receptor. Simultaneous treatment with HGF and EGF elicited an increase in proliferation, dispersion, degradation of extracellular matrix, and motility. Following EGF treatment, BME-UV mammary cells exhibited an increase in MET expression at both the mRNA and protein levels. Long-term treatment of BME-UV cells with HGF and EGF together increased the level of activation of the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathways when compared with HGF or EGF alone. These data outline a possible cooperative role of the EGF and HGF pathways and indicate that cross-talk between their respective receptors may modulate mammary gland development in the cow.