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001-es BibID:BIBFORM103424
035-os BibID:(WOS)000837443600001 (Scopus)85134360196
Első szerző:Jdeed, Sham
Cím:The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling / Jdeed Sham, Erdős Edina, Bálint Bálint L., Uray Iván P.
Dátum:2022
ISSN:1541-7786
Megjegyzések:Gaining pharmacologic access to the potential of ARID1A, a tumor suppressor protein, to mediate transcriptional control over cancer gene expression is an unresolved challenge. Retinoid X receptor ligands are pleiotropic, incompletely understood tools that regulate breast epithelial cell proliferation and differentiation. We found that low-dose bexarotene (Bex) combined with the nonselective beta-blocker carvedilol (Carv) reduces proliferation of MCF10DCIS.com cells and markedly suppresses ARID1A levels. Similarly, Carv synergized with Bex in MCF-7 cells to suppress cell growth. Chromatin immunoprecipitation sequencing analysis revealed that under nonestrogenic conditions Bex ? Carv alters the concerted genomic distribution of the chromatin remodeler ARID1A and acetylated histone H3K27, at sites related to insulinlike growth factor (IGF) signaling. Several distinct sites of ARID1A enrichment were identified in the IGF-1 receptor and IRS1 genes, associated with a suppression of both proteins. The knock-down of ARID1A increased IGF-1R levels, prevented IGF-1R and IRS1 suppression upon Bex ? Carv, and stimulated proliferation. In vitro IGF-1 receptor neutralizing antibody suppressed cell growth, while elevated IGF-1R or IRS1 expression was associated with poor survival of patients with ER-negative breast cancer. Our study demonstrates direct impact of ARID1A redistribution on the expression and growth regulation of IGF-1? related genes, induced by repurposed clinical drugs under nonestrogenic conditions.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
ARID1A
IGF-I
rexinoid
growth suppression
Megjelenés:Molecular Cancer Research. - 20 : 7 (2022), p. 1071-1082. -
További szerzők:Erdős Edina (1989-) (klinikai laboratóriumi kutató) Bálint Bálint László (1971-) (kutató orvos) Uray Iván Péter (1970-) (kutatóorvos)
Pályázati támogatás:NKFIH-K129218
OTKA
GINOP-2.3.2-15-2016-00020
GINOP
EFOP-3.6.1-16-2016-00022
EFOP
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