Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/122318
Title: | Bromodomain inhibition shows antitumoral activity in mice and human luminal breast cancer |
Author: | Pérez Salvia, Montserrat Simó-Riudalbas, Laia Llinàs-Arias, Pere Roa, Laura Setién, Fernando Soler, Marta Castro de Moura, Manuel Bradner, James E. González Suárez, Eva Moutinho, Cátia Esteller, Manel |
Keywords: | Tumors Ratolins (Animals de laboratori) Càncer de mama Tumors Mice (Laboratory animals) Breast cancer |
Issue Date: | 29-May-2017 |
Publisher: | Impact Journals |
Abstract: | BET bromodomain inhibitors, which have an antitumoral effect against various solid cancer tumor types, have not been studied in detail in luminal breast cancer, despite the prevalence of this subtype of mammary malignancy. Here we demonstrate that the BET bromodomain inhibitor JQ1 exerts growth-inhibitory activity in human luminal breast cancer cell lines associated with a depletion of the C-MYC oncogene, but does not alter the expression levels of the BRD4 bromodomain protein. Interestingly, expression microarray analyses indicate that, upon JQ1 administration, the antitumoral phenotype also involves downregulation of relevant breast cancer oncogenes such as the Breast Carcinoma-Amplified Sequence 1 (BCAS1) and the PDZ Domain-Containing 1 (PDZK1). We have also applied these in vitro findings in an in vivo model by studying a transgenic mouse model representing the luminal B subtype of breast cancer, the MMTV-PyMT, in which the mouse mammary tumor virus promoter is used to drive the expression of the polyoma virus middle T-antigen to the mammary gland. We have observed that the use of the BET bromodomain inhibitor for the treatment of established breast neoplasms developed in the MMTV-PyMT model shows antitumor potential. Most importantly, if JQ1 is given before the expected time of tumor detection in the MMTV-PyMT mice, it retards the onset of the disease and increases the survival of these animals. Thus, our findings indicate that the use of bromodomain inhibitors is of great potential in the treatment of luminal breast cancer and merits further investigation. |
Note: | Reproducció del document publicat a: https://doi.org/10.18632/oncotarget.18255 |
It is part of: | Oncotarget, 2017, vol. 8, num. 31, p. 51621-51629 |
URI: | http://hdl.handle.net/2445/122318 |
Related resource: | https://doi.org/10.18632/oncotarget.18255 |
ISSN: | 1949-2553 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Articles publicats en revistes (Ciències Fisiològiques) |
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