Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme.
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults. It is known that amplification of the epidermal growth factor receptor gene (EGFR) occurs in approximately 40% of GBM, leading to enhanced activation of the EGFR signaling pathway and promoting tumor growth. Although...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5608330?pdf=render |
| _version_ | 1818948166947438592 |
|---|---|
| author | Doreen William Poroshista Mokri Nora Lamp Michael Linnebacher Carl Friedrich Classen Andreas Erbersdobler Björn Schneider |
| author_facet | Doreen William Poroshista Mokri Nora Lamp Michael Linnebacher Carl Friedrich Classen Andreas Erbersdobler Björn Schneider |
| author_sort | Doreen William |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults. It is known that amplification of the epidermal growth factor receptor gene (EGFR) occurs in approximately 40% of GBM, leading to enhanced activation of the EGFR signaling pathway and promoting tumor growth. Although GBM mutations are stably maintained in GBM in vitro models, rapid loss of EGFR gene amplification is a common observation during cell culture. To maintain EGFR amplification in vitro, heterotopic GBM xenografts with elevated EGFR copy number were cultured under varying serum conditions and EGF concentrations. EGFR copy numbers were assessed over several passages by quantitative PCR and chromogenic in situ hybridization. As expected, in control assays with 10% FCS, cells lost EGFR amplification with increasing passage numbers. However, cells cultured under serum free conditions stably maintained elevated copy numbers. Furthermore, EGFR protein expression positively correlated with genomic amplification levels. Although elevated EGFR copy numbers could be maintained over several passages in vitro, levels of EGFR amplification were variable and dependent on the EGF concentration in the medium. In vitro cultures of GBM cells with elevated EGFR copy number and corresponding EGFR protein expression should prove valuable preclinical tools to gain a better understanding of EGFR driven glioblastoma and assist in the development of new improved therapies. |
| first_indexed | 2024-12-20T08:42:29Z |
| format | Article |
| id | doaj.art-cae944101865406ea978a71e069f4136 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T08:42:29Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cae944101865406ea978a71e069f41362022-12-21T19:46:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018520810.1371/journal.pone.0185208Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme.Doreen WilliamPoroshista MokriNora LampMichael LinnebacherCarl Friedrich ClassenAndreas ErbersdoblerBjörn SchneiderGlioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults. It is known that amplification of the epidermal growth factor receptor gene (EGFR) occurs in approximately 40% of GBM, leading to enhanced activation of the EGFR signaling pathway and promoting tumor growth. Although GBM mutations are stably maintained in GBM in vitro models, rapid loss of EGFR gene amplification is a common observation during cell culture. To maintain EGFR amplification in vitro, heterotopic GBM xenografts with elevated EGFR copy number were cultured under varying serum conditions and EGF concentrations. EGFR copy numbers were assessed over several passages by quantitative PCR and chromogenic in situ hybridization. As expected, in control assays with 10% FCS, cells lost EGFR amplification with increasing passage numbers. However, cells cultured under serum free conditions stably maintained elevated copy numbers. Furthermore, EGFR protein expression positively correlated with genomic amplification levels. Although elevated EGFR copy numbers could be maintained over several passages in vitro, levels of EGFR amplification were variable and dependent on the EGF concentration in the medium. In vitro cultures of GBM cells with elevated EGFR copy number and corresponding EGFR protein expression should prove valuable preclinical tools to gain a better understanding of EGFR driven glioblastoma and assist in the development of new improved therapies.http://europepmc.org/articles/PMC5608330?pdf=render |
| spellingShingle | Doreen William Poroshista Mokri Nora Lamp Michael Linnebacher Carl Friedrich Classen Andreas Erbersdobler Björn Schneider Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme. PLoS ONE |
| title | Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme. |
| title_full | Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme. |
| title_fullStr | Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme. |
| title_full_unstemmed | Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme. |
| title_short | Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme. |
| title_sort | amplification of the egfr gene can be maintained and modulated by variation of egf concentrations in in vitro models of glioblastoma multiforme |
| url | http://europepmc.org/articles/PMC5608330?pdf=render |
| work_keys_str_mv | AT doreenwilliam amplificationoftheegfrgenecanbemaintainedandmodulatedbyvariationofegfconcentrationsininvitromodelsofglioblastomamultiforme AT poroshistamokri amplificationoftheegfrgenecanbemaintainedandmodulatedbyvariationofegfconcentrationsininvitromodelsofglioblastomamultiforme AT noralamp amplificationoftheegfrgenecanbemaintainedandmodulatedbyvariationofegfconcentrationsininvitromodelsofglioblastomamultiforme AT michaellinnebacher amplificationoftheegfrgenecanbemaintainedandmodulatedbyvariationofegfconcentrationsininvitromodelsofglioblastomamultiforme AT carlfriedrichclassen amplificationoftheegfrgenecanbemaintainedandmodulatedbyvariationofegfconcentrationsininvitromodelsofglioblastomamultiforme AT andreaserbersdobler amplificationoftheegfrgenecanbemaintainedandmodulatedbyvariationofegfconcentrationsininvitromodelsofglioblastomamultiforme AT bjornschneider amplificationoftheegfrgenecanbemaintainedandmodulatedbyvariationofegfconcentrationsininvitromodelsofglioblastomamultiforme |