GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors.
Bmi1 is a member of the polycomb repressive complex 1 and plays different roles during embryonic development, depending on the developmental context. Bmi1 over expression is observed in many types of cancer, including tumors of astroglial and neural origin. Although genetic depletion of Bmi1 has bee...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035943&type=printable |
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| author | Bart A Westerman Marleen Blom Ellen Tanger Martin van der Valk Ji-Ying Song Marije van Santen Jules Gadiot Paulien Cornelissen-Steijger John Zevenhoven Haydn M Prosser Anthony Uren Eleonora Aronica Maarten van Lohuizen |
| author_facet | Bart A Westerman Marleen Blom Ellen Tanger Martin van der Valk Ji-Ying Song Marije van Santen Jules Gadiot Paulien Cornelissen-Steijger John Zevenhoven Haydn M Prosser Anthony Uren Eleonora Aronica Maarten van Lohuizen |
| author_sort | Bart A Westerman |
| collection | DOAJ |
| description | Bmi1 is a member of the polycomb repressive complex 1 and plays different roles during embryonic development, depending on the developmental context. Bmi1 over expression is observed in many types of cancer, including tumors of astroglial and neural origin. Although genetic depletion of Bmi1 has been described to result in tumor inhibitory effects partly through INK4A/Arf mediated senescence and apoptosis and also through INK4A/Arf independent effects, it has not been proven that Bmi1 can be causally involved in the formation of these tumors. To see whether this is the case, we developed two conditional Bmi1 transgenic models that were crossed with GFAP-Cre mice to activate transgenic expression in neural and glial lineages. We show here that these mice generate intermediate and anterior lobe pituitary tumors that are positive for ACTH and beta-endorphin. Combined transgenic expression of Bmi1 together with conditional loss of Rb resulted in pituitary tumors but was insufficient to induce medulloblastoma therefore indicating that the oncogenic function of Bmi1 depends on regulation of p16(INK4A)/Rb rather than on regulation of p19(ARF)/p53. Human pituitary adenomas show Bmi1 overexpression in over 50% of the cases, which indicates that Bmi1 could be causally involved in formation of these tumors similarly as in our mouse model. |
| format | Article |
| id | doaj-art-6af8facbcc884638a76bf0cd182d6c29 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-6af8facbcc884638a76bf0cd182d6c292025-08-20T02:08:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3594310.1371/journal.pone.0035943GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors.Bart A WestermanMarleen BlomEllen TangerMartin van der ValkJi-Ying SongMarije van SantenJules GadiotPaulien Cornelissen-SteijgerJohn ZevenhovenHaydn M ProsserAnthony UrenEleonora AronicaMaarten van LohuizenBmi1 is a member of the polycomb repressive complex 1 and plays different roles during embryonic development, depending on the developmental context. Bmi1 over expression is observed in many types of cancer, including tumors of astroglial and neural origin. Although genetic depletion of Bmi1 has been described to result in tumor inhibitory effects partly through INK4A/Arf mediated senescence and apoptosis and also through INK4A/Arf independent effects, it has not been proven that Bmi1 can be causally involved in the formation of these tumors. To see whether this is the case, we developed two conditional Bmi1 transgenic models that were crossed with GFAP-Cre mice to activate transgenic expression in neural and glial lineages. We show here that these mice generate intermediate and anterior lobe pituitary tumors that are positive for ACTH and beta-endorphin. Combined transgenic expression of Bmi1 together with conditional loss of Rb resulted in pituitary tumors but was insufficient to induce medulloblastoma therefore indicating that the oncogenic function of Bmi1 depends on regulation of p16(INK4A)/Rb rather than on regulation of p19(ARF)/p53. Human pituitary adenomas show Bmi1 overexpression in over 50% of the cases, which indicates that Bmi1 could be causally involved in formation of these tumors similarly as in our mouse model.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035943&type=printable |
| spellingShingle | Bart A Westerman Marleen Blom Ellen Tanger Martin van der Valk Ji-Ying Song Marije van Santen Jules Gadiot Paulien Cornelissen-Steijger John Zevenhoven Haydn M Prosser Anthony Uren Eleonora Aronica Maarten van Lohuizen GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors. PLoS ONE |
| title | GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors. |
| title_full | GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors. |
| title_fullStr | GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors. |
| title_full_unstemmed | GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors. |
| title_short | GFAP-Cre-mediated transgenic activation of Bmi1 results in pituitary tumors. |
| title_sort | gfap cre mediated transgenic activation of bmi1 results in pituitary tumors |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035943&type=printable |
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