Cargando…

Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures

BACKGROUND: Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment....

Descripción completa

Detalles Bibliográficos
Autores principales: Adrien, Daigeler, Ludger, Klein-Hitpass, Michael, Chromik Ansgar, Oliver, Müller, Jörg, Hauser, Heinz-Herbert, Homann, Hans-Ulrich, Steinau, Marcus, Lehnhardt
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585096/
https://www.ncbi.nlm.nih.gov/pubmed/18959781
http://dx.doi.org/10.1186/1471-2407-8-313
_version_ 1782160837655396352
author Adrien, Daigeler
Ludger, Klein-Hitpass
Michael, Chromik Ansgar
Oliver, Müller
Jörg, Hauser
Heinz-Herbert, Homann
Hans-Ulrich, Steinau
Marcus, Lehnhardt
author_facet Adrien, Daigeler
Ludger, Klein-Hitpass
Michael, Chromik Ansgar
Oliver, Müller
Jörg, Hauser
Heinz-Herbert, Homann
Hans-Ulrich, Steinau
Marcus, Lehnhardt
author_sort Adrien, Daigeler
collection PubMed
description BACKGROUND: Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment. METHODS: Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique. RESULTS: A variety of genes involved in apoptosis were up and down regulated in different samples revealing a heterogeneous expression pattern of the 19 primary tumor cell cultures in response to doxorubicin treatment. However, more than 50% of the samples showed up-regulation of pro-apoptotic genes such as TRAIL Receptor2, CDKN1A, GADD45A, FAS, CD40, PAWR, NFKBIA, IER3, PSEN1, RIPK2, and CD44. The anti-apoptotic genes TNFAIP3, PEA15, Bcl2A1, NGFB, and BIRC3 were also up-regulated. The pro-apoptotic CD14, TIA1, and ITGB2 were down-regulated in more than 50% of the tumor cultures after treatment with doxorubicin, as was the antiapoptotic YWHAH. CONCLUSION: Despite a correlation of the number of differentially regulated genes to the tumor grading and to a lesser extent histological subtype, the expression patterns varied strongly; however, especially among high grade tumors the responses of selected apoptosis genes were similar. The predescribed low clinical response rates of low grade liposarcoma to doxorubicin correspond to our results with only little changes on gene expression level and also divergent findings concerning the up- and down-regulation of single genes in the different sarcoma samples.
format Text
id pubmed-2585096
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-25850962008-11-20 Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures Adrien, Daigeler Ludger, Klein-Hitpass Michael, Chromik Ansgar Oliver, Müller Jörg, Hauser Heinz-Herbert, Homann Hans-Ulrich, Steinau Marcus, Lehnhardt BMC Cancer Research Article BACKGROUND: Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment. METHODS: Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique. RESULTS: A variety of genes involved in apoptosis were up and down regulated in different samples revealing a heterogeneous expression pattern of the 19 primary tumor cell cultures in response to doxorubicin treatment. However, more than 50% of the samples showed up-regulation of pro-apoptotic genes such as TRAIL Receptor2, CDKN1A, GADD45A, FAS, CD40, PAWR, NFKBIA, IER3, PSEN1, RIPK2, and CD44. The anti-apoptotic genes TNFAIP3, PEA15, Bcl2A1, NGFB, and BIRC3 were also up-regulated. The pro-apoptotic CD14, TIA1, and ITGB2 were down-regulated in more than 50% of the tumor cultures after treatment with doxorubicin, as was the antiapoptotic YWHAH. CONCLUSION: Despite a correlation of the number of differentially regulated genes to the tumor grading and to a lesser extent histological subtype, the expression patterns varied strongly; however, especially among high grade tumors the responses of selected apoptosis genes were similar. The predescribed low clinical response rates of low grade liposarcoma to doxorubicin correspond to our results with only little changes on gene expression level and also divergent findings concerning the up- and down-regulation of single genes in the different sarcoma samples. BioMed Central 2008-10-29 /pmc/articles/PMC2585096/ /pubmed/18959781 http://dx.doi.org/10.1186/1471-2407-8-313 Text en Copyright © 2008 Adrien et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Adrien, Daigeler
Ludger, Klein-Hitpass
Michael, Chromik Ansgar
Oliver, Müller
Jörg, Hauser
Heinz-Herbert, Homann
Hans-Ulrich, Steinau
Marcus, Lehnhardt
Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures
title Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures
title_full Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures
title_fullStr Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures
title_full_unstemmed Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures
title_short Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures
title_sort heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585096/
https://www.ncbi.nlm.nih.gov/pubmed/18959781
http://dx.doi.org/10.1186/1471-2407-8-313
work_keys_str_mv AT adriendaigeler heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures
AT ludgerkleinhitpass heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures
AT michaelchromikansgar heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures
AT olivermuller heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures
AT jorghauser heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures
AT heinzherberthomann heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures
AT hansulrichsteinau heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures
AT marcuslehnhardt heterogeneousinvitroeffectsofdoxorubicinongeneexpressioninprimaryhumanliposarcomacultures