Misbehaviour of XIST RNA in breast cancer cells.

A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controve...

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Main Authors: Silvia M Sirchia, Silvia Tabano, Laura Monti, Maria P Recalcati, Manuela Gariboldi, Francesca R Grati, Giovanni Porta, Palma Finelli, Paolo Radice, Monica Miozzo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2679222?pdf=render
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author Silvia M Sirchia
Silvia Tabano
Laura Monti
Maria P Recalcati
Manuela Gariboldi
Francesca R Grati
Giovanni Porta
Palma Finelli
Paolo Radice
Monica Miozzo
author_facet Silvia M Sirchia
Silvia Tabano
Laura Monti
Maria P Recalcati
Manuela Gariboldi
Francesca R Grati
Giovanni Porta
Palma Finelli
Paolo Radice
Monica Miozzo
author_sort Silvia M Sirchia
collection DOAJ
description A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors.
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spelling doaj.art-e5c6d90db3a44161a64582235d29e6972022-12-22T03:58:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0145e555910.1371/journal.pone.0005559Misbehaviour of XIST RNA in breast cancer cells.Silvia M SirchiaSilvia TabanoLaura MontiMaria P RecalcatiManuela GariboldiFrancesca R GratiGiovanni PortaPalma FinelliPaolo RadiceMonica MiozzoA role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors.http://europepmc.org/articles/PMC2679222?pdf=render
spellingShingle Silvia M Sirchia
Silvia Tabano
Laura Monti
Maria P Recalcati
Manuela Gariboldi
Francesca R Grati
Giovanni Porta
Palma Finelli
Paolo Radice
Monica Miozzo
Misbehaviour of XIST RNA in breast cancer cells.
PLoS ONE
title Misbehaviour of XIST RNA in breast cancer cells.
title_full Misbehaviour of XIST RNA in breast cancer cells.
title_fullStr Misbehaviour of XIST RNA in breast cancer cells.
title_full_unstemmed Misbehaviour of XIST RNA in breast cancer cells.
title_short Misbehaviour of XIST RNA in breast cancer cells.
title_sort misbehaviour of xist rna in breast cancer cells
url http://europepmc.org/articles/PMC2679222?pdf=render
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