PMID- 19156217
OWN - NLM
STAT- MEDLINE
DCOM- 20090515
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 1
DP  - 2009
TI  - Polycomb group protein Bmi1 is required for growth of RAF driven non-small-cell 
      lung cancer.
PG  - e4230
LID - 10.1371/journal.pone.0004230 [doi]
LID - e4230
AB  - BACKGROUND: 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. PRINCIPAL 
      FINDINGS: 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). SIGNIFICANCE: The data identifies Bmi1 as an 
      important factor for expansion but not initiation of RAF driven NSCLC.
FAU - Becker, Matthias
AU  - Becker M
AD  - Bayerisches Krebsforschungszentrum, University of Wuerzburg, Wuerzburg, Germany.
FAU - Korn, Christian
AU  - Korn C
FAU - Sienerth, Arnold R
AU  - Sienerth AR
FAU - Voswinckel, Robert
AU  - Voswinckel R
FAU - Luetkenhaus, Katharina
AU  - Luetkenhaus K
FAU - Ceteci, Fatih
AU  - Ceteci F
FAU - Rapp, Ulf R
AU  - Rapp UR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090119
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Bmi1 protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tumor Suppressor Protein p14ARF)
RN  - EC 2.3.2.27 (Polycomb Repressive Complex 1)
RN  - EC 2.7.11.1 (raf Kinases)
SB  - IM
MH  - Animals
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism
MH  - Cell Transformation, Neoplastic
MH  - Crosses, Genetic
MH  - Cyclin-Dependent Kinase Inhibitor p16/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Lung/metabolism
MH  - Lung Neoplasms/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Models, Genetic
MH  - Nuclear Proteins/genetics/*physiology
MH  - Polycomb Repressive Complex 1
MH  - Proto-Oncogene Proteins/genetics/*physiology
MH  - Repressor Proteins/genetics/*physiology
MH  - Tumor Suppressor Protein p14ARF/metabolism
MH  - raf Kinases/*metabolism
PMC - PMC2626631
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/01/22 09:00
MHDA- 2009/05/16 09:00
PMCR- 2009/01/19
CRDT- 2009/01/22 09:00
PHST- 2008/08/05 00:00 [received]
PHST- 2008/12/05 00:00 [accepted]
PHST- 2009/01/22 09:00 [entrez]
PHST- 2009/01/22 09:00 [pubmed]
PHST- 2009/05/16 09:00 [medline]
PHST- 2009/01/19 00:00 [pmc-release]
AID - 08-PONE-RA-05834R1 [pii]
AID - 10.1371/journal.pone.0004230 [doi]
PST - ppublish
SO  - PLoS One. 2009;4(1):e4230. doi: 10.1371/journal.pone.0004230. Epub 2009 Jan 19.