The peptide hormone prolactin (PRL) and certain members of the epidermal growth factor (EGF) family play central roles in mammary gland development and physiology, and their dysregulation has been implicated in mammary tumorigenesis. Our recent studies have revealed that the CUB and zona pellucida-like domain-containing protein 1 (CUZD1) is a critical factor for PRL-mediated activation of the transcription factor STAT5 in mouse mammary epithelium. Of note, CUZD1 controls production of a specific subset of the EGF family growth factors and consequent activation of their receptors. Here, we found that consistent with this finding, CUZD1 overexpression in non-transformed mammary epithelial HC11 cells increases their proliferation and induces tumorigenic characteristics in these cells. When introduced orthotopically in mouse mammary glands, these cells formed adenocarcinomas, exhibiting elevated levels of STAT5 phosphorylation and activation of the EGF signaling pathway. Selective blockade of STAT5 phosphorylation by pimozide, a small-molecule inhibitor, markedly reduced the production of the EGF family growth factors and inhibited PRL-induced tumor cell proliferation in vitro. Pimozide administration to mice also suppressed CUZD1-driven mammary tumorigenesis in vivo. Analysis of human MCF7 breast cancer cells indicated that CUZD1 controls the production of the same subset of EGF family members in these cells as in the mouse. Moreover, pimozide treatment reduced the proliferation of these cancer cells. Collectively, these findings indicate that overexpression of CUZD1, a regulator of growth factor pathways controlled by PRL and STAT5, promotes mammary tumorigenesis. Blockade of the STAT5 signaling pathway downstream of CUZD1 may offer a therapeutic strategy for managing these breast tumors.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ENjq8G
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Pycnodysostosis is a rare autosomal, recessive, skeletal dysplasia caused by a mutation in the cathepsin k gene. Pycnodysostosis is characte...
-
2016-12-10T02-17-59Z Source: Indo American Journal of Pharmaceutical Research Radha S & Sreelatha .S*. Research has demonstrated th...
-
ACS Nano DOI: 10.1021/acsnano.7b01783 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2trY7nv via...
-
2016-10-22T03-07-52Z Source: International Journal of Community Medicine and Public Health Ketan R. Dagdiya, Sushma S. Thakre, Subhash B....
-
Need Industrial relations advice? Unfair dismissals laws? Discrimination in the workplace? Sexual harassment? We can help. AWNA is Australia...
-
by Javier U. Chicote, Rob DeSalle, José Segarra, Tung-Tien Sun, Antonio García-España from #AlexandrosSfakianakis via Alexandros G.Sfakia...
-
Vol.28 No.1 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1QLVDop via IFTTT
-
Participant Experiences of Attending a Community CBT Workshop for Insomnia: A Qualitative Six-Year Follow-Up. Behav Sleep Med. 2017 Ap...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου