HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells
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 m...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-03-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317695028 |
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| author | Krisha Desai Radhika Aiyappa Jyothi S Prabhu Madhumathy G Nair Patrick Varun Lawrence Aruna Korlimarla Anupama CE Annie Alexander Rohini S Kaluve Suraj Manjunath Marjorrie Correa BS Srinath Shekhar Patil Anjali Kalamdani MSN Prasad TS Sridhar |
| author_facet | Krisha Desai Radhika Aiyappa Jyothi S Prabhu Madhumathy G Nair Patrick Varun Lawrence Aruna Korlimarla Anupama CE Annie Alexander Rohini S Kaluve Suraj Manjunath Marjorrie Correa BS Srinath Shekhar Patil Anjali Kalamdani MSN Prasad TS Sridhar |
| author_sort | Krisha Desai |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8e7c7acd668d44bc94926d906faa46c6 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-8e7c7acd668d44bc94926d906faa46c62025-08-20T03:33:45ZengSAGE PublishingTumor Biology1423-03802017-03-013910.1177/1010428317695028HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cellsKrisha Desai0Radhika Aiyappa1Jyothi S Prabhu2Madhumathy G Nair3Patrick Varun Lawrence4Aruna Korlimarla5Anupama CE6Annie Alexander7Rohini S Kaluve8Suraj Manjunath9Marjorrie Correa10BS Srinath11Shekhar Patil12Anjali Kalamdani13MSN Prasad14TS Sridhar15Division of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaSt. John’s Medical College Hospital, Bangalore, IndiaSt. John’s Medical College Hospital, Bangalore, IndiaSri Shankara Cancer Hospital and Research Centre, Bangalore, IndiaSri Shankara Cancer Hospital and Research Centre, Bangalore, IndiaSri Shankara Cancer Hospital and Research Centre, Bangalore, IndiaSri Shankara Cancer Hospital and Research Centre, Bangalore, IndiaDivision of Molecular Medicine, St. John’s Research Institute, St. John’s National Academy of Health Sciences, Bangalore, IndiaDespite 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.https://doi.org/10.1177/1010428317695028 |
| spellingShingle | Krisha Desai Radhika Aiyappa Jyothi S Prabhu Madhumathy G Nair Patrick Varun Lawrence Aruna Korlimarla Anupama CE Annie Alexander Rohini S Kaluve Suraj Manjunath Marjorrie Correa BS Srinath Shekhar Patil Anjali Kalamdani MSN Prasad TS Sridhar HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells Tumor Biology |
| title | HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells |
| title_full | HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells |
| title_fullStr | HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells |
| title_full_unstemmed | HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells |
| title_short | HR+HER2− breast cancers with growth factor receptor–mediated EMT have a poor prognosis and lapatinib downregulates EMT in MCF-7 cells |
| title_sort | hr her2 breast cancers with growth factor receptor mediated emt have a poor prognosis and lapatinib downregulates emt in mcf 7 cells |
| url | https://doi.org/10.1177/1010428317695028 |
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