Version 1
: Received: 11 September 2024 / Approved: 11 September 2024 / Online: 11 September 2024 (16:23:00 CEST)
How to cite:
Eccleshall, W. B.; Mung, K. L.; Laiho, I.-M.; Sahlgren, C. M.; Koskinen, P. J. PIM Kinases Regulate Estrogen Receptor α Signaling in Luminal A Breast Cancer Cells. Preprints2024, 2024090907. https://doi.org/10.20944/preprints202409.0907.v1
Eccleshall, W. B.; Mung, K. L.; Laiho, I.-M.; Sahlgren, C. M.; Koskinen, P. J. PIM Kinases Regulate Estrogen Receptor α Signaling in Luminal A Breast Cancer Cells. Preprints 2024, 2024090907. https://doi.org/10.20944/preprints202409.0907.v1
Eccleshall, W. B.; Mung, K. L.; Laiho, I.-M.; Sahlgren, C. M.; Koskinen, P. J. PIM Kinases Regulate Estrogen Receptor α Signaling in Luminal A Breast Cancer Cells. Preprints2024, 2024090907. https://doi.org/10.20944/preprints202409.0907.v1
APA Style
Eccleshall, W. B., Mung, K. L., Laiho, I. M., Sahlgren, C. M., & Koskinen, P. J. (2024). PIM Kinases Regulate Estrogen Receptor α Signaling in Luminal A Breast Cancer Cells. Preprints. https://doi.org/10.20944/preprints202409.0907.v1
Chicago/Turabian Style
Eccleshall, W. B., Cecilia M. Sahlgren and Päivi J. Koskinen. 2024 "PIM Kinases Regulate Estrogen Receptor α Signaling in Luminal A Breast Cancer Cells" Preprints. https://doi.org/10.20944/preprints202409.0907.v1
Abstract
Estrogen receptor α (ERα) is a nuclear hormone receptor that mediates the biological effects of estrogen and is known to be phosphorylated at multiple sites. Despite several reports highlighting serine-167 (S167) of ERα as a common phosphorylation site for various kinases, there have been contradictory data regarding its relevance in the context of ERα-expressing luminal A breast cancer. In this study, we show that S167 is targeted by the oncogenic PIM family kinases in these cells. Loss of PIM expression or catalytic activity reduces S167 phosphorylation and restricts ERα signaling, while PIM overexpression has the opposite effect. Nonetheless, we found no evidence that PIMs protect breast cancer cells from ERα blockade, as both PIM protein levels and ERα S167 phosphorylation levels were substantially lower in populations of cells that had developed tamoxifen resistance as compared to untreated cells. However, this does not rule out the possibility that PIMs provide protection against ERα-targeting therapies in such breast cancer cells in which they are overexpressed, warranting further investigations.
Keywords
PIM kinases; estrogen receptor α; luminal A breast cancer; targeted therapy resistance
Subject
Biology and Life Sciences, Life Sciences
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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