Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
| Autor: | Emily J. Gallagher, Tiffany Scully, Nathan Kase, Derek LeRoith |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
MAPK/ERK pathway
MAP Kinase Signaling System Science Cell Triple Negative Breast Neoplasms Transfection Ribosomal Protein S6 Kinases 90-kDa Article Mice Breast cancer Cell Line Tumor Nitriles Butadienes medicine Animals Humans Gene Silencing RNA Messenger Epidermal growth factor receptor Phosphorylation Receptor Triple-negative breast cancer Multidisciplinary Epidermal Growth Factor biology Chemistry Growth factor signalling nutritional and metabolic diseases Cancer medicine.disease ErbB Receptors medicine.anatomical_structure Receptors LDL LDL receptor Cancer research biology.protein Medicine Female lipids (amino acids peptides and proteins) Mitogen-Activated Protein Kinases Signal transduction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
| ISSN: | 2045-2322 |
| Popis: | Expression of the low-density lipoprotein receptor (LDLR) has been shown to play a critical role in hypercholesterolemia-associated breast cancer growth and is associated with shorter recurrence-free survival in human breast cancer studies. We sought to identify how circulating LDL cholesterol and tumor LDLR might accelerate oncogenic processes by determining whether increased LDLR expression and cholesterol uptake are associated with the activation of the epidermal growth factor receptor (EGFR) signaling pathway in triple negative breast cancer (TNBC) cell lines. EGF stimulation of MDA-MB-468 (MDA468) cells activated p44/42MAPK (MAPK), increased expression of LDLR, and fluorescent LDL cholesterol uptake. However, stimulation of MDA-MB-231 (MDA231) cells with EGF did not lead to increased expression of LDLR despite inducing phosphorylation of EGFR. Inhibition of MAPK using UO126 in MDA231 cells reduced LDLR expression, and in MDA468 cells, UO126 impaired the LDLR increase in response to EGF. MDA468 cells exposed to the transcription inhibitor, Actinomycin, prior to treatment with EGF showed reduced degradation of LDLR mRNA compared to vehicle-treated cells. Our results suggest that the EGF-associated increase in LDLR protein expression is cell line-specific. The common pathway regulating LDLR expression was MAPK in both TNBC cell lines. |
| Databáze: | OpenAIRE |
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