Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line

BACKGROUND: Reprimo (RPRM), a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to charac...

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Autores principales: Buchegger,Kurt, Ili,Carmen, Riquelme,Ismael, Letelier,Pablo, Corvalán,Alejandro H., Brebi,Priscilla, Huang,Tim Hui-Ming, Roa,Juan Carlos
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2016
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602016000100005
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spelling oai:scielo:S0716-976020160001000052016-12-01Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell lineBuchegger,KurtIli,CarmenRiquelme,IsmaelLetelier,PabloCorvalán,Alejandro H.Brebi,PriscillaHuang,Tim Hui-MingRoa,Juan Carlos Reprimo MDA-MB-231 Migration Invasion BACKGROUND: Reprimo (RPRM), a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to characterize the epigenetic inactivation and its biological function in BC cell lines. METHODS: The correlation between RPRM methylation and loss of mRNA expression was assessed in six breast cancer cell lines by methylation specific PCR (MSP), 5'-Aza-2'-deoxycytidine treatment and RT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of RPRM in cell proliferation, cell cycle, cell death, cell migration and invasion. RESULTS: In the cancer methylome system (CMS) (web-based system for visualizing and analyzing genome-wide methylation data of human cancers), the CpG island region of RPRM (1.1 kb) was hypermethylated in breast cancer compared to normal breast tissue; more interesting still was that ERa(+) tumors showed higher methylation intensity than ERa(-). Downregulation of RPRM mRNA by methylation was confirmed in MDA-MB-231 and BT-20 cell lines. In addition, overexpression of RPRM in MDA-MB-231 cells resulted in decreased rates of cell migration, wound healing and invasion in vitro. However, RPRM overexpression did not alter cell viability, phosphatidylserine (PS) translocation or G2/M cell cycle transition. CONCLUSION: Taken together, these data suggest that RPRM is involved in decreased cell migration and invasion in vitro, acting as a potential tumor suppressor gene in the MDA-MB-231 cell line.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.49 20162016-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602016000100005en10.1186/s40659-016-0066-7
institution Scielo Chile
collection Scielo Chile
language English
topic Reprimo
MDA-MB-231
Migration
Invasion
spellingShingle Reprimo
MDA-MB-231
Migration
Invasion
Buchegger,Kurt
Ili,Carmen
Riquelme,Ismael
Letelier,Pablo
Corvalán,Alejandro H.
Brebi,Priscilla
Huang,Tim Hui-Ming
Roa,Juan Carlos
Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line
description BACKGROUND: Reprimo (RPRM), a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to characterize the epigenetic inactivation and its biological function in BC cell lines. METHODS: The correlation between RPRM methylation and loss of mRNA expression was assessed in six breast cancer cell lines by methylation specific PCR (MSP), 5'-Aza-2'-deoxycytidine treatment and RT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of RPRM in cell proliferation, cell cycle, cell death, cell migration and invasion. RESULTS: In the cancer methylome system (CMS) (web-based system for visualizing and analyzing genome-wide methylation data of human cancers), the CpG island region of RPRM (1.1 kb) was hypermethylated in breast cancer compared to normal breast tissue; more interesting still was that ERa(+) tumors showed higher methylation intensity than ERa(-). Downregulation of RPRM mRNA by methylation was confirmed in MDA-MB-231 and BT-20 cell lines. In addition, overexpression of RPRM in MDA-MB-231 cells resulted in decreased rates of cell migration, wound healing and invasion in vitro. However, RPRM overexpression did not alter cell viability, phosphatidylserine (PS) translocation or G2/M cell cycle transition. CONCLUSION: Taken together, these data suggest that RPRM is involved in decreased cell migration and invasion in vitro, acting as a potential tumor suppressor gene in the MDA-MB-231 cell line.
author Buchegger,Kurt
Ili,Carmen
Riquelme,Ismael
Letelier,Pablo
Corvalán,Alejandro H.
Brebi,Priscilla
Huang,Tim Hui-Ming
Roa,Juan Carlos
author_facet Buchegger,Kurt
Ili,Carmen
Riquelme,Ismael
Letelier,Pablo
Corvalán,Alejandro H.
Brebi,Priscilla
Huang,Tim Hui-Ming
Roa,Juan Carlos
author_sort Buchegger,Kurt
title Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line
title_short Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line
title_full Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line
title_fullStr Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line
title_full_unstemmed Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line
title_sort reprimo as a modulator of cell migration and invasion in the mda-mb-231 breast cancer cell line
publisher Sociedad de Biología de Chile
publishDate 2016
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602016000100005
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