RETRACTED: Epigenetic control of endothelin-1 axis affects invasiveness of breast carcinoma cells with bone tropism
Authors: Paola Bendinelli
Paola Maroni
Maria Alfonsina Desiderio
Alessia Locatelli
Emanuela Matteucci
Journal: Experimental Cell Research (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Endothelin-1; Epigenetic reactions; Bone metastatic cells; Breast carcinoma; Histone deacetylases
Affiliations: Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, via Luigi Mangiagalli, 31, 20133 Milano, Italy., Istituto Ortopedico Galeazzi, IRCCS, Milano, Italy., Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, via Luigi Mangiagalli, 31, 20133 Milano, Italy; Istituto FIRC di Oncologia Molecolare, Milano, Italy., Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, via Luigi Mangiagalli, 31, 20133 Milano, Italy. Electronic address: .

Abstract:  Here, we report a complex regulation of endothelin-1 (ET-1) axis driven by epigenetic reactions in 1833-bone metastatic cells, emphasizing the importance in skeletal metastasis from breast carcinoma. Inhibitors of histone deacetylases, trichostatin A (TSA), and of DNA methylases, 5'-Azacytidine (Aza), caused, respectively, reduction and increase in 1833 cell invasiveness, without affecting the basal migration of parental MDA-MB231 cells. Of note, in the two cell lines exposed to Aza the blockade of the ET-1 receptor ETAR with BQ-123 oppositely changed invasive properties. Even if in MDA-MB231 cells the ET-1 axis was scarcely influenced by epigenetic reactions, ETAR remarkably decreased after Aza. In contrast, in 1833 cells Aza exposure enhanced ET-1 coupled to ETAR wild type, being also ETAR truncated form increased, and invasiveness was stimulated. Under demethylation, the increase in ET-1 steady state protein level in 1833 clone seemed regulated at transcriptional level principally via Ets1 transcription factor. In fact, actinomycin D almost completely prevented ET-1 mRNA induction due to Aza. Only in 1833 cells, TSA exposure inactivated ET-1 axis, with reduction of the expression of ET-1 and ETAR mutated form, in agreement with Matrigel invasion decrease. This treatment favoured the ET-1 repressional control, taking place at the level of mRNA stability due to the 3'-untranslated region in the ET-1 gene, and also decreased transcription via NF-kB. Environmental conditions that alter the balance between epigenetic reactions might, therefore, affect metastasis migratory mode influencing ET-1 axis. 

Retracted: Yes

PubPeer comments:
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 - Figure 4C BBA 1813 and Figure 5 Mol Cancer Res 7, 1328 For HDAC1 and HDAC3 we reported our results in the two papers (Mol Cancer Res 7 and BBA 1813). So, also the vinculins are repeated - The other vinculins in the yellow and blue squares are not the same bands undergoing vertical or horizontal flips (Figure 5 Carcinogenesis 30, Figure 1B BBA 1843, Figure 2 European J Cancer 49). -HDAC1, Figure 5 Mol Cancer Res: when you compare the original pictures in the two articles, it is possible to appreciate that the 3 evidenced (yellow) bands are not the same of those in Figure 5 Carcinogenesis. In fact, in the original pictures they show different thickness. HDAC3, Figure 5 Mol Cancer Res: the vinculins shows some differences from those of Figure 2A BBRC. By simple observation, in Figure5 Carcinogenesis 30, the two bands indicated (red) do not seem stretched; the flip of the bands in blue and green squares is difficult to discern (Carcinogenesis 30 vs. Figure 1B BBA 1843 and Figure 1B Exp Cell Res 319). , 
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 This paper, Exp Cell Res. 2013 Jul 15;319(12):1865-74, is in the South East. ![file] , 
 Figs 3A, 3C. Could the authors check to confirm that the ET-1 2-day Control and ET-1 30-day Control blots are not the same image, accidentally flipped and re-used? ![file] , 
 Part of Figure 4E. ![file] Already regretting accepting Clippy s offer of assistance in preparing an image of Matrigel invasion assay. UPDATE: More Matrigel invasion assays from Figs 3B, 3D. ![file] , 
 Here are the panels of Fig 3D, rotated through 90 deg., annotated as above. ![] They also appear as two panels of Fig 4E in [Matteucci et al (2013)] with different cell-number counts. ![] , 
 Missed one in Fig 4E![file] , 
 #9 I missed lots. ![file] , 
 2020 retraction. https: www.sciencedirect.com science article pii S0014482720304201?via%3Dihub This article has been retracted at the request of the Editor-in-Chief and the authors as lanes of Fig. 1 are similar with lanes of Fig. 5 of this article and Fig. 4B of the article that the authors have published in the Journal of Cellular Physiology 174 (1998) 125u2013134 https: doi.org 10.1002 (SICI)1097-4652(199801)174:1 125::AID-JCP14 3.0.CO;2-E. , 
 #11 Unfortunately no mention of the artistic merits of those assays. ,