Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3.
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Embargo End Date
ICR Authors
Authors
Box, C
Pennington, C
Hare, S
Porter, S
Edwards, D
Eccles, S
Crompton, M
Harvey, A
Pennington, C
Hare, S
Porter, S
Edwards, D
Eccles, S
Crompton, M
Harvey, A
Document Type
Journal Article
Date
2023-06-28
Date Accepted
2023-06-23
Abstract
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.
Citation
International Journal of Molecular Sciences, 2023, 24 (13), pp. 10757 -
Source Title
International Journal of Molecular Sciences
Publisher
MDPI
ISSN
1422-0067
eISSN
1422-0067
Collections
Research Team
Radiother Phys Modelling