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638408.pdf (1.25 MB)

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2012-07

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cc-by (c) Romero, Octavio A. et al., 2012
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126140

The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer

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Recurs relacionat

https://doi.org/10.1002/emmm.201200236

Resum

BRG1, a member of the SWI/SNF complex, is mutated in cancer, but it is unclear how it promotes tumourigenesis. We report that re-expression of BRG1 in lung cancer cells up-regulates lung-specific transcripts, restoring the gene expression signature of normal lung. Using cell lines from several cancer types we found that those lacking BRG1 do not respond to retinoic acid (RA) or glucocorticoids (GC), while restoration of BRG1 restores sensitivity. Conversely, in SH-SY5Y cells, a paradigm of RA-dependent differentiation, abrogation of BRG1 prevented the response to RA. Further, our data suggest an antagonistic functional connection between BRG1 and MYC, whereby, refractoriness to RA and GC by BRG1 inactivation involves deregulation of MYC activity. Mechanistically, some of these effects are mediated by BRG1 binding to MYC and MYC-target promoters. The BRG1-MYC antagonism was also evident in primary tumours. Finally, BRG1 restoration significantly dampened invasion and progression and decreased MYC in lung cancer cells orthotopically implanted in nude mice. Thus, BRG1 inactivation enables cancer cells to sustain undifferentiated gene expression programs and prevent its response to environmental stimuli.

Matèries

Càncer de pulmó, Mutació (Biologia), Expressió gènica

Matèries (anglès)

Lung cancer, Mutation (Biology), Gene expression

Citació

Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

ROMERO FERRARO, Octavio, et al. The tumour suppressor and chromatin-remodelling factor BRG1 antagonizes Myc activity and promotes cell differentiation in human cancer. EMBO Molecular Medicine. 2012. Vol. 4, num. 7, pags. 603-616. ISSN 1757-4676. [consulted: 4 of August of 2026]. Available at: https://hdl.handle.net/2445/126140

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