Cisplatin sensitivity in breast cancer cells is associated with particular DMTF1 splice variant expression.

Niklaus, Nicolas Jan; Humbert, Magali; Tschan, Mario (2018). Cisplatin sensitivity in breast cancer cells is associated with particular DMTF1 splice variant expression. Biochemical and biophysical research communications, 503(4), pp. 2800-2806. Academic Press 10.1016/j.bbrc.2018.08.042

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The cyclin D binding myb-like transcription factor 1 (DMTF1) is a tumor suppressor gene that activates p14 transcription and thereby stabilizing the p53 tumor suppressor. The DMTF1 gene locus encodes for three different alternatively spliced isoforms, namely DMTF1α, β and γ. The oncogenic DMTF1β isoform negatively interferes with the transcriptional activity of DMTF1α. Increased DMTF1β is associated with increased cell proliferation in a variety of cancer cell types. In this study, we aimed at identifying the role of DMTF1 isoforms in response to cisplatin treatment in breast cancer cells. First, we used SKBR3 (cisplatin sensitive) and MCF7 (cisplatin resistant) breast cancer cell lines to quantify DMTF1 expression in response to cisplatin treatment. Total DMTF1 mRNA levels increased in a dose dependent manner in both cell lines upon cisplatin treatment. However, the mRNA levels of the isoforms revealed that the sensitive cell line, SKBR3, showed increased levels of both isoforms, whereas the resistant cell, MCF7, only showed increased levels of the oncogenic DMTF1β isoform. Silencing all DMTF1 isoforms led to increased cell survival upon cisplatin treatment. Furthermore, we found a significant increase in the percentage of quiescent cells in SKBR3 shDMTF1. Together, our data suggest that DMTF1 expression levels are associated with increased cisplatin resistance.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Niklaus, Nicolas Jan; Humbert, Magali and Tschan, Mario

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0006-291X

Publisher:

Academic Press

Language:

English

Submitter:

Mario Tschan

Date Deposited:

27 Aug 2018 11:29

Last Modified:

23 Oct 2019 08:01

Publisher DOI:

10.1016/j.bbrc.2018.08.042

PubMed ID:

30100063

Uncontrolled Keywords:

Cisplatin DMTF1 Splice variant hDMP1

BORIS DOI:

10.7892/boris.119551

URI:

https://boris.unibe.ch/id/eprint/119551

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