The cyclin D binding myb-like transcription factor 1 (DMTF1) is a tumor suppressor gene that activates p14(ARF) transcription and thereby stabilizing the p53 tumor suppressor. The DMTF1 gene locus encodes for three different alternatively spliced isoforms, namely DMTF1 alpha, beta and gamma The oncogenic DMTF1 beta isoform negatively interferes with the transcriptional activity of DMTF1 alpha. Increased DMTF1 beta 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 DMTF1 beta 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. (C) 2018 Elsevier Inc. All rights reserved.