BAG3 interacts with p53 in endometrial carcinoma
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LETTER TO THE EDITOR
BAG3 interacts with p53 in endometrial carcinoma Margot De Marco 1,2 & Jacopo Troisi 1,3,4 & Luigi Giugliano 1 & Alessandra Rosati 1,2 & Antonio D’Antonio 1 & Roberta Iaccarino 1 & Mario Capunzo 1 & Francesco Salzano 1 & Rosanna Martinelli 1 & Pierpaolo Cavallo 5 & Maurizio Guida 3,6 & Liberato Marzullo 1,2 Accepted: 15 June 2020 # International Society for Cellular Oncology 2020
Dear Editor, BAG3 (74 kDa) belongs to a family of proteins sharing a BAG domain, which interacts with the heat shock protein (HSP) 70 and regulates its activity. BAG3 can also bind to other proteins through its WW domain, proline-rich (PXXP) region and IPV (Ile-Pro-Val) motif. Due to its interactions with several partner proteins, BAG3 has been found to regulate diverse cellular processes, including autophagy, mechanotransduction, cytoskeleton organization, cell motility, cell cycle progression and apoptosis [1]. BAG3 is also constitutively expressed in some tumors, where it contributes to sustaining cell survival and proliferation [1, 2]. BAG3 has been found to be expressed in human endometrial carcinomas [3]. A putative trait of these tumors is a lack of p53 activity, due to mutations and/or allelic loss of its gene or to increased expression of its negative regulators, such as MDM2 [4]. To investigate the involvement of BAG3 in endometrial carcinoma development, we first assessed the expression of Margot De Marco and Jacopo Troisi, Maurizio Guida and Liberato Marzullo contributed equally to this work. * Margot De Marco [email protected] 1
Department of Medicine, Surgery and Odontology “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, SA, Italy
2
BIOUNIVERSA s.r.l., R&D Division, 84081 Baronissi, SA, Italy
3
Theoreo srl – Spin-off Company of the University of Salerno, Salerno, Italy
4
European Biomedical Research Institute of Salerno EBRIS, 84125 Salerno, Italy
5
Department of Physics, University of Salerno, 84084 Fisciano, SA, Italy
6
Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy
its protein in human primary benign endometrial hyperplasias (BEH), atypical endometrial hyperplasias (AEH) and AEHs associated with endometrial cancer (EC). In addition, we assessed the interaction of BAG3 with p53 in the human endometrial carcinoma cell line Ishikawa [5]. We used immunohistochemistry (IHC) to assess BAG3 expression in removed uterine polyps from 94 patients (age range: 26–84 years; mean age: 54.7 years) with diagnoses of: benign endometrial hyperplasia (BEH, 48 patients), atypical endometrial hyperplasia (AEH, 33 patients) and AEH associated with endometrial cancer (13 patients). We scored the samples based on the level of intensity and extent of staining, using a 3-point scale (0 = no visible staining; 1 = low positivity; 2 = high positivity). BAG3 expression could not be detected in BEH (mean IHC score: 0.00), while it was detectable in AEH, either associated or not asso
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