Back to Search
Start Over
HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells
- Source :
- Tumor Biology, Vol 39 (2017)
- Publication Year :
- 2017
- Publisher :
- IOS Press, 2017.
-
Abstract
- Despite an overall good prognosis, a significant proportion of patients with hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers develop distant metastases. The metastatic potential of epithelial cells is known to be regulated by tumor–stromal interaction and mediated by epithelial-to-mesenchymal transition. Hormone receptor positive human epidermal growth factor receptor 2 negative tumors were used to estimate markers of epithelial-to-mesenchymal transition, and the luminal breast cancer cell line MCF-7 was used to examine the interactions between integrins and growth factor receptors in causation of epithelial-to-mesenchymal transition. A total of 140 primary tumors were sub-divided into groups enriched for the markers of epithelial-to-mesenchymal transition (snail family transcriptional repressor 2 and integrin β6) versus those with low levels. Within the epithelial-to-mesenchymal transition+ tumors, there was a positive correlation between the transcripts of integrin β6 and growth factor receptors—human epidermal growth factor receptor 2 and epidermal growth factor receptor. In tumors enriched for epithelial-to-mesenchymal transition markers, patients with tumors with the highest quartile of growth factor receptor transcripts had a shorter disease-free survival compared to patients with low growth factor receptor expression by Kaplan–Meier analysis (log rank, p = 0.03). Epithelial-to-mesenchymal transition was induced in MCF-7 cells by treatment with transforming growth factor beta 1 and confirmed by upregulation of SNAI1 and SNAI2 transcripts, increase of vimentin and integrin β6 protein, and repression of E-cadherin. Treatment of these cells with the dual-specificity tyrosine-kinase inhibitor lapatinib led to downregulation of epithelial-to-mesenchymal transition as indicated by lower levels of SNAI1 and SNAI2 transcripts, integrin αvβ6, and matrix metalloproteinase 9 protein. The results suggest that synergistic interactions between growth factor receptors and integrin β6 could mediate epithelial-to-mesenchymal transition and migration in a subset of luminal breast cancers and lapatinib might be effective in disrupting this interaction.
- Subjects :
- 0301 basic medicine
Oncology
Integrins
medicine.medical_specialty
Poor prognosis
Epithelial-Mesenchymal Transition
Receptor, ErbB-2
Breast Neoplasms
Kaplan-Meier Estimate
Lapatinib
Disease-Free Survival
Metastasis
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Breast cancer
Growth factor receptor
Antigens, Neoplasm
Internal medicine
Biomarkers, Tumor
medicine
Humans
Epithelial–mesenchymal transition
RC254-282
Aged
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
General Medicine
Middle Aged
Cadherins
medicine.disease
Gene Expression Regulation, Neoplastic
030104 developmental biology
Matrix Metalloproteinase 9
MCF-7
Hormone receptor
030220 oncology & carcinogenesis
MCF-7 Cells
Quinazolines
Female
Snail Family Transcription Factors
business
medicine.drug
Subjects
Details
- ISSN :
- 14230380 and 10104283
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Tumor Biology
- Accession number :
- edsair.doi.dedup.....f744b79785c18185c5710cf3d16bc74f