Protein secretion in human mammary epithelial cells following HER1 receptor activation: influence of HER2 and HER3 expression
Open Access
- 14 February 2011
- journal article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 11 (1), 69
- https://doi.org/10.1186/1471-2407-11-69
Abstract
Background Protein secretion by mammary cells results in autocrine and paracrine signaling that defines cell growth, migration and the extracellular environment. Even so, we have a limited understanding of the cellular processes that regulate protein secretion. Methods In this study, we utilize human epithelial mammary cell (HMEC) lines that were engineered to express different levels of HER1, HER2 and HER3. Using an ELISA microarray platform, we evaluate the effects of epidermal growth factor family receptor (HER) expression on protein secretion in the HMEC lines upon initiation of HER1 receptor activation. The secreted proteins include three HER1 ligands, interleukins 1α and 18, RANTES, vascular-endothelial and platelet-derived growth factors, matrix metalloproteases 1, 2 and 9, and the extracellular portion of the HER1 and HER2 proteins. In addition, we investigate whether MAPK/Erk and PI3K/Akt signaling regulate protein secretion in these cell lines and if so, whether the involvement of HER2 or HER3 receptor alters their response to MAPK/Erk and PI3K/Akt signal pathway inhibition in terms of protein secretion. Results Differential expression of HER2 and HER3 receptors alters the secretion of a variety of growth factors, cytokines, and proteases. Some alterations in protein secretion are still observed when MAPK/Erk or PI3K/Akt signaling is inhibited. Conclusion This study suggests that HER overexpression orchestrates broad changes in the tumor microenvironment by altering the secretion of a diverse variety of biologically active proteins.Keywords
This publication has 71 references indexed in Scilit:
- HER/ErbB receptor interactions and signaling patterns in human mammary epithelial cellsBMC Cell Biology, 2009
- The multiplex bead array approach to identifying serum biomarkers associated with breast cancerBreast Cancer Research, 2009
- Multiple Mechanisms Are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial CellsOnline Journal of Public Health Informatics, 2008
- Quantifying the effects of co-expressing EGFR and HER2 on HER activation and traffickingBiochemical and Biophysical Research Communications, 2008
- A collection of breast cancer cell lines for the study of functionally distinct cancer subtypesCancer Cell, 2006
- The ErbB receptors and their role in cancer progressionExperimental Cell Research, 2003
- New functions for the matrix metalloproteinases in cancer progressionNature Reviews Cancer, 2002
- EGFR and cancer prognosisEuropean Journal of Cancer, 2001
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Role of the Insulin-Like Growth Factor Family in Cancer Development and ProgressionJNCI Journal of the National Cancer Institute, 2000