Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.

We have previously described a RAF oncogene driven transgenic mouse model for non small cell lung cancer (NSCLC). Here we examine whether tumor initiation and growth requires the stem cell self-renewal factor Bmi1.In order to evaluate Bmi1 function in NSCLC two founder lines that differ in incidence...

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Main Authors: Matthias Becker, Christian Korn, Arnold R Sienerth, Robert Voswinckel, Katharina Luetkenhaus, Fatih Ceteci, Ulf R Rapp
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2626631?pdf=render
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author Matthias Becker
Christian Korn
Arnold R Sienerth
Robert Voswinckel
Katharina Luetkenhaus
Fatih Ceteci
Ulf R Rapp
author_facet Matthias Becker
Christian Korn
Arnold R Sienerth
Robert Voswinckel
Katharina Luetkenhaus
Fatih Ceteci
Ulf R Rapp
author_sort Matthias Becker
collection DOAJ
description We have previously described a RAF oncogene driven transgenic mouse model for non small cell lung cancer (NSCLC). Here we examine whether tumor initiation and growth requires the stem cell self-renewal factor Bmi1.In order to evaluate Bmi1 function in NSCLC two founder lines that differ in incidence and latency of tumor formation were compared. Ablation of Bmi1 expression in both lines had a dramatically decreased tumor growth. As the line with shorter latency matched the life span of Bmi1 knock out mice, these mice were chosen for further study. The absence of Bmi1 did not decrease the number of tumor initiation in these mice as only the size and not the number of tumors decreased. Reduction in tumor growth resulted from an increase in cell death and decrease in cell cycle progression that corresponded with up-regulation of the p16(INK4a) and p19(ARF).The data identifies Bmi1 as an important factor for expansion but not initiation of RAF driven NSCLC.
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spelling doaj.art-13158d7ea5a74b919d852c6308d2c9482022-12-22T01:32:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0141e423010.1371/journal.pone.0004230Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.Matthias BeckerChristian KornArnold R SienerthRobert VoswinckelKatharina LuetkenhausFatih CeteciUlf R RappWe have previously described a RAF oncogene driven transgenic mouse model for non small cell lung cancer (NSCLC). Here we examine whether tumor initiation and growth requires the stem cell self-renewal factor Bmi1.In order to evaluate Bmi1 function in NSCLC two founder lines that differ in incidence and latency of tumor formation were compared. Ablation of Bmi1 expression in both lines had a dramatically decreased tumor growth. As the line with shorter latency matched the life span of Bmi1 knock out mice, these mice were chosen for further study. The absence of Bmi1 did not decrease the number of tumor initiation in these mice as only the size and not the number of tumors decreased. Reduction in tumor growth resulted from an increase in cell death and decrease in cell cycle progression that corresponded with up-regulation of the p16(INK4a) and p19(ARF).The data identifies Bmi1 as an important factor for expansion but not initiation of RAF driven NSCLC.http://europepmc.org/articles/PMC2626631?pdf=render
spellingShingle Matthias Becker
Christian Korn
Arnold R Sienerth
Robert Voswinckel
Katharina Luetkenhaus
Fatih Ceteci
Ulf R Rapp
Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.
PLoS ONE
title Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.
title_full Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.
title_fullStr Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.
title_full_unstemmed Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.
title_short Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell lung cancer.
title_sort polycomb group protein bmi1 is required for growth of raf driven non small cell lung cancer
url http://europepmc.org/articles/PMC2626631?pdf=render
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