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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...

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Autores principales: Box, Carol, Pennington, Caroline, Hare, Stephen, Porter, Sarah, Edwards, Dylan, Eccles, Suzanne, Crompton, Mark, Harvey, Amanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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