Potential role of the HOXD8 transcription factor in cisplatin resistance and tumour metastasis in advanced epithelial ovarian cancer.

Abstract:

:Few studies have examined the potential transcription factor (TF) simultaneously associated with cisplatin resistance and metastasis in ovarian cancer. To assess a related mechanism, a 345-channel protein/DNA array and transcriptional activity ELISA were performed to compare the TF activities in the cisplatin-sensitive SKOV3 and cisplatin-resistant SKOV3-DDP cells and in HO-8910 and the homologous highly metastatic HO-8910PM cells. In SKOV3-DDP vs. SKOV3 cells, 43 TFs were up-regulated, while 31 were down-regulated. In HO-8910PM vs. HO-8910 cells, 13 TFs were up-regulated, while 18 were down-regulated. In these two models, 4 TFs (HOXD8(1), HOXD8(2), RB, RFX1/2/3) were simultaneously up-regulated, and 9 TFs (SRE, FKHR, Angiotensinogen ANG-IRE, Pax2, CD28RC/NF-IL2B, HLF, CPE, CBFB and c-Ets-1) were down-regulated. HOXD8 mRNA and protein expression levels measured by reverse transcription polymerase chain reaction and ELISA, respectively, were significantly higher in SKOV3-DDP and HO-8910PM than in their corresponding cell lines (both p < 0.05). In 52 cases of different ovarian disease, the patients with recurrent and cisplatin-resistant ovarian cancer had higher expression levels of HOXD8 than patients with primary malignant tumours (p = 0.018, p = 0.001) or benign tumours (p = 0.001, p < 0.001). Taken together, these results suggest that HOXD8 is potentially associated with both cisplatin resistance and metastasis in advanced ovarian cancer.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Sun P,Song Y,Liu D,Liu G,Mao X,Dong B,Braicu EI,Sehouli J

doi

10.1038/s41598-018-31030-3

subject

Has Abstract

pub_date

2018-09-07 00:00:00

pages

13483

issue

1

issn

2045-2322

pii

10.1038/s41598-018-31030-3

journal_volume

8

pub_type

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