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Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3
The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte d...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341933/ https://www.ncbi.nlm.nih.gov/pubmed/37445934 http://dx.doi.org/10.3390/ijms241310757 |
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author | Box, Carol Pennington, Caroline Hare, Stephen Porter, Sarah Edwards, Dylan Eccles, Suzanne Crompton, Mark Harvey, Amanda |
author_facet | Box, Carol Pennington, Caroline Hare, Stephen Porter, Sarah Edwards, Dylan Eccles, Suzanne Crompton, Mark Harvey, Amanda |
author_sort | Box, Carol |
collection | PubMed |
description | The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived ‘evolutionary history’. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract. We found that involucrin, a keratinocyte differentiation marker, was expressed in a high proportion (78%) of breast carcinoma samples and cell lines. Interestingly, tumour samples found to express high levels of involucrin were also shown to express Brk. 1,25-dihydroxyvitamin D3, a known differentiation agent and potential anti-cancer agent, decreased proliferation in the breast cancer cell lines that expressed both involucrin and Brk, whereas the Brk/involucrin negative cell lines tested were less susceptible. In addition, responses to 1,25-dihydroxyvitamin D3 were not correlated with vitamin D receptor expression. These data contribute to the growing body of evidence suggesting that cellular responses to 1,25-dihydroxyvitamin D3 are potentially independent of vitamin D receptor status and provide an insight into potential markers, such as Brk and/or involucrin that could predict therapeutic responses to 1,25-dihydroxyvitamin D3. |
format | Online Article Text |
id | pubmed-10341933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103419332023-07-14 Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3 Box, Carol Pennington, Caroline Hare, Stephen Porter, Sarah Edwards, Dylan Eccles, Suzanne Crompton, Mark Harvey, Amanda Int J Mol Sci Article The process of human embryonic mammary development gives rise to the structures in which mammary cells share a developmental lineage with skin epithelial cells such as keratinocytes. As some breast carcinomas have previously been shown to express high levels of involucrin, a marker of keratinocyte differentiation, we hypothesised that some breast tumours may de-differentiate to a keratinocyte-derived ‘evolutionary history’. To confirm our hypothesis, we investigated the frequency of involucrin expression along with that of Brk, a tyrosine kinase expressed in up to 86% of breast carcinomas whose normal expression patterns are restricted to differentiating epithelial cells, most notably those in the skin (keratinocytes) and the gastrointestinal tract. We found that involucrin, a keratinocyte differentiation marker, was expressed in a high proportion (78%) of breast carcinoma samples and cell lines. Interestingly, tumour samples found to express high levels of involucrin were also shown to express Brk. 1,25-dihydroxyvitamin D3, a known differentiation agent and potential anti-cancer agent, decreased proliferation in the breast cancer cell lines that expressed both involucrin and Brk, whereas the Brk/involucrin negative cell lines tested were less susceptible. In addition, responses to 1,25-dihydroxyvitamin D3 were not correlated with vitamin D receptor expression. These data contribute to the growing body of evidence suggesting that cellular responses to 1,25-dihydroxyvitamin D3 are potentially independent of vitamin D receptor status and provide an insight into potential markers, such as Brk and/or involucrin that could predict therapeutic responses to 1,25-dihydroxyvitamin D3. MDPI 2023-06-28 /pmc/articles/PMC10341933/ /pubmed/37445934 http://dx.doi.org/10.3390/ijms241310757 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Box, Carol Pennington, Caroline Hare, Stephen Porter, Sarah Edwards, Dylan Eccles, Suzanne Crompton, Mark Harvey, Amanda Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3 |
title | Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3 |
title_full | Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3 |
title_fullStr | Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3 |
title_full_unstemmed | Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3 |
title_short | Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3 |
title_sort | brk/ptk6 and involucrin expression may predict breast cancer cell responses to vitamin d3 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341933/ https://www.ncbi.nlm.nih.gov/pubmed/37445934 http://dx.doi.org/10.3390/ijms241310757 |
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