| Title |
Regulatory crosstalk of doxorubicin, estradiol and TNF alpha combined treatment in breast cancer-derived cell lines / |
| Authors |
Nassiri, Isar ; Inga, Alberto ; Meškytė, Erna Marija ; Alessandrini, Federica ; Ciribilli, Yari ; Priami, Corrado |
| DOI |
10.1038/s41598-019-51349-9 |
| Full Text |
|
| Is Part of |
Scientific reports.. London : Nature Publishing Group. 2019, vol. 9, art. no.15172, p. [1-11].. eISSN 2045-2322 |
| Keywords [eng] |
estrogen-receptor-alpha ; enrichment analysis ; P53 ; resistance ; transactivation ; mechanisms ; apoptosis ; pathways ; models ; growth |
| Abstract [eng] |
We present a new model of ESR1 network regulation based on analysis of Doxorubicin, Estradiol, and TNF alpha combination treatment in MCF-7. We used Doxorubicin as a therapeutic agent, TNF alpha as marker and mediator of an inflammatory microenvironment and 17 beta-Estradiol (E2) as an agonist of Estrogen Receptors, known predisposing factor for hormone-driven breast cancer, whose pharmacological inhibition reduces the risk of breast cancer recurrence. Based on the results of transcriptomics analysis, we found 71 differentially expressed genes that are specific for the combination treatment with Doxorubicin +Estradiol +TNF alpha in comparison with single or double treatments. The responsiveness to the triple treatment was examined for seven genes by qPCR, of which six were validated, and then extended to four additional cell lines differing for p53 and/or ER status. The results of differential regulation enrichment analysis highlight the role of the ESR1 network that included 36 of 71 specific differentially expressed genes. We propose that the combined activation of p53 and NF-kappa B transcription factors significantly influences ligand-dependent, ER-driven transcriptional responses, also of the ESR1 gene itself. These results provide a model of coordinated interaction of TFs to explain the Doxorubicin, E2 and TNF alpha induced repression mechanisms. |
| Published |
London : Nature Publishing Group |
| Type |
Journal article |
| Language |
English |
| Publication date |
2019 |
