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Updated: Oct 20, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Expression of c-erbB-4/HER4 is regulated in T47D breast carcinoma cells by retinoids and vitamin D3
M Offterdinger1, S M Schneider, H Huber
1Laboratory for Cell Growth, Division of Oncology, University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
Abstract:
Nuclear steroid/retinoid and memgbrane c-erbB receptor tyrosine kinase signaling control proliferation and differentiation of mammary epithelial cells. Recently, we reported that retinoic acids are efficient repressors of c-erbB-2 and -3, but not of c-erbB-1 gene expresson. Here we demonstrate that retinoid acid- mediated growth inhibition is accompanied with reduced expression of c-erbB-4/HER4 in T47D breast cancer cells as determined by FACS, Western, and RT-PCR. All-trans and 9-cis retinoic acid reduce c-erbB-4 expression to 30%-60% of control, depending on the concentration. Dexamethasone (Dex) is inactive on D3 (D3), in contrast, acts as a strong inducer, elevation more that twofold at the mRNA, but does not significantly affect cell growth. We concolude that retinoic acids are efficient growth inhibitors and repressors of cell growth and c-erbB-4, whereas D3 represents a highly efficient inducer of c-erbB-4 expression with affecting cell proliferation.
Insights
Retinoic acids inhibit breast cancer cell growth by reducing c-erbB-4/HER4 expression. Dexamethasone (Dex) induces c-erbB-4/HER4 without affecting cell proliferation, highlighting distinct signaling pathways.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- Nuclear steroid/retinoid and membrane c-erbB receptor tyrosine kinase signaling pathways regulate mammary epithelial cell proliferation and differentiation.
- Retinoic acids were previously identified as repressors of c-erbB-2 and -3 gene expression.
Purpose of the Study:
- To investigate the effect of retinoid acid on c-erbB-4/HER4 expression in T47D breast cancer cells.
- To compare the effects of retinoic acid and dexamethasone (Dex) on c-erbB-4/HER4 expression and cell growth.
Main Methods:
- Flow cytometry (FACS)
- Western blotting
- Reverse transcription polymerase chain reaction (RT-PCR)
- Cell proliferation assays
Main Results:
- Retinoic acid significantly reduced c-erbB-4/HER4 expression in T47D cells by 30%-60% in a dose-dependent manner.
- Dexamethasone (Dex) strongly induced c-erbB-4/HER4 mRNA levels (more than twofold) but did not significantly affect cell growth.
- Retinoic acid demonstrated potent growth inhibitory effects alongside the repression of c-erbB-4/HER4.
Conclusions:
- Retinoic acids act as effective inhibitors of breast cancer cell growth and repressors of c-erbB-4/HER4 expression.
- Dexamethasone (Dex) is a potent inducer of c-erbB-4/HER4 expression without impacting cell proliferation, indicating distinct regulatory mechanisms.
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