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Brk/PTK6 and Involucrin Expression May Predict Breast Cancer Cell Responses to Vitamin D3

Authors :
Carol Box
Caroline Pennington
Stephen Hare
Sarah Porter
Dylan Edwards
Suzanne Eccles
Mark Crompton
Amanda Harvey
Source :
International Journal of Molecular Sciences, Vol 24, Iss 13, p 10757 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

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.

Details

Language :
English
ISSN :
24131075, 14220067, and 16616596
Volume :
24
Issue :
13
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.53c6907a7218416bbadbea6b36e8fd0a
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms241310757