2026-04-17T15:46:35Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1223182025-12-05T09:25:05Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Pérez Salvia, Montserrat author Simó-Riudalbas, Laia author Llinàs-Arias, Pere author Roa, Laura author Setién, Fernando author Soler, Marta author Castro de Moura, Manuel author Bradner, James E. author González Suárez, Eva author Moutinho, Cátia author Esteller, Manel author 2018-05-14T07:12:35Z 2018-05-14T07:12:35Z 2017-05-29 2018-05-14T07:12:36Z 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. Tumors Ratolins (Animals de laboratori) Càncer de mama Tumors Mice (Laboratory animals) Breast cancer Bromodomain inhibition shows antitumoral activity in mice and human luminal breast cancer