Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-7391
Authors: Bicker, Anne
Brahmer, Alexandra
Meller, Sebastian
Kristiansen, Glen
Gorr, Thomas A.
Hankeln, Thomas
Title: The distinct gene regulatory network of myoglobin in prostate and breast cancer
Online publication date: 13-Jul-2022
Language: english
Abstract: Myoglobin (MB) is not only strongly expressed in myocytes, but also at much lower levels in different cancer entities. 40% of breast tumors are MB-positive, with the globin being co-expressed with markers of tumor hypoxia in a proportion of cases. In breast cancer, MB expression is associated with a positive hormone receptor status and patient prognosis. In prostate cancer, another hormone-dependent cancer type, 53% of tumors were recently shown to express MB. Especially in more aggressive prostate cancer specimen MB expression also correlates with increased patient survival rates. Both findings might be due to tumor-suppressing properties of MB in cancer cells. In contrast to muscle, MB transcription in breast and prostate cancer mainly depends on a novel, alternative promoter site. We show here that its associated transcripts can be upregulated by hypoxia and downregulated by estrogens and androgens in MCF7 breast and LNCaP prostate cancer cells, respectively. Bioinformatic data mining of epigenetic histone marks and experimental verification reveal a hitherto uncharacterized transcriptional network that drives the regulation of the MB gene in cancer cells. We identified candidate hormone-receptor binding elements that may interact with the cancer-associated MB promoter to decrease its activity in breast and prostate cancer cells. Additionally, a regulatory element, 250 kb downstream of the promoter, acts as a hypoxia-inducible site within the transcriptional machinery. Understanding the distinct regulation of MB in tumors will improve unraveling the respiratory protein’s function in the cancer context and may provide new starting points for developing therapeutic strategies.
DDC: 570 Biowissenschaften
570 Life sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 02 Sozialwiss., Medien u. Sport
FB 10 Biologie
Place: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-7391
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
Information on rights of use: https://creativecommons.org/licenses/by/4.0/
Journal: PLoS one
10
11
Pages or article number: e0142662
Publisher: PLoS
Publisher place: Lawrence, Kan.
Issue date: 2015
ISSN: 1932-6203
Publisher URL: http://dx.doi.org/10.1371/journal.pone.0142662
Publisher DOI: 10.1371/journal.pone.0142662
Appears in collections:DFG-OA-Publizieren (2012 - 2017)

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