Influence of Terminal Differentiation and PACAP on the Cytokine, Chemokine, and Growth Factor Secretion of Mammary Epithelial Cells

• Published in: Journal of molecular neuroscience Vol. 52; no. 1; pp. 28 - 36
• Main Authors: Csanaky, Katalin, Doppler, Wolfgang, Tamas, Andrea, Kovacs, Krisztina, Toth, Gabor, Reglodi, Dora
• Format: Journal Article
• Language: English
• Published: Boston Springer US 2014; Springer Nature B.V
• Subjects: Amphiregulin; Angiogenesis; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Breastfeeding & lactation; Caseins - genetics; Caseins - metabolism; Cell Biology; Cell Differentiation; Cell growth; Cell Line; Chemokine CCL5 - genetics; Chemokine CCL5 - metabolism; Chemokine CXCL10 - genetics; Chemokine CXCL10 - metabolism; Chemokines; Cytokines; EGF Family of Proteins; Epidermal growth factor; Epidermal Growth Factor - genetics; Epidermal Growth Factor - metabolism; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Glycoproteins - genetics; Glycoproteins - metabolism; Growth Substances - pharmacology; Hormones; Influence; Insulin; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-like growth factors; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Kinases; Ligands; Lymphocytes; Mammary Glands, Animal - cytology; Mice; Nervous system; Neuroblastoma; Neurochemistry; Neurology; Neuropeptides; Neurosciences; p38 Mitogen-Activated Protein Kinases - metabolism; Pituitary Adenylate Cyclase-Activating Polypeptide - pharmacology; Polypeptides; Proteins; Proteomics; Proto-Oncogene Proteins c-akt - metabolism; STAT5 Transcription Factor - metabolism; Stem cells; Hungary; Mammary differentiation; PACAP; IP-10; Amphiregulin; RANTES; EGF
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-013-0193-3

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with trophic and cytoprotective effects, has been shown to affect cell survival, proliferation, and also differentiation of various cell types. The high PACAP level in the milk and its changes during lactation suggest a possible effect of PACAP on the differentiation of mammary epithelial cells. Mammary cell differentiation is regulated by hormones, growth factors, cytokines/chemokines, and angiogenic proteins. In this study, differentiation was hormonally induced by lactogenic hormones in confluent cultures of HC11 mouse mammary epithelial cells. We investigated the effect of PACAP on mammary cell differentiation as well as release of cytokines, chemokines, and growth factors. Differentiation was assessed by expression analysis of the milk protein β-casein. Differentiation significantly decreased the secretion of interferon gammainduced protein (IP)-10, “regulated upon activation normal T cell expressed and presumably secreted” (RANTES), insulin-like growth factor-binding protein (IGFBP)-3 and the epidermal growth factor receptor (EGFR) ligands, such as epidermal growth factor (EGF) and amphiregulin (AREG). The changes in the levels of IP-10 and RANTES may be relevant for the alterations in homing of T cells and B cells at different stages of mammary gland development, while the changes of the EGFR ligands may facilitate the switch from proliferative to lactating stage. PACAP did not modulate the expression of β-casein or the activity of hormone-induced pathways as determined by the analysis of phosphorylation of Akt, STAT5, and p38 MAPK. However, PACAP decreased the release of EGF and AREG from non-differentiated cells. This may influence the extracellular signal-related transactivation of EGFR in the non-differentiated mammary epithelium and is considered to have an impact on the modulation of oncogenic EGFR signaling in breast cancer.