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


RESULTS
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).


CONCLUSIONS
The data identifies Bmi1 as an important factor for expansion but not initiation of RAF driven NSCLC.
Becker
Matthias
M
Bayerisches Krebsforschungszentrum, University of Wuerzburg, Wuerzburg, Germany.
Korn
Christian
C
Sienerth
Arnold R
AR
Voswinckel
Robert
R
Luetkenhaus
Katharina
K
Ceteci
Fatih
F
Rapp
Ulf R
UR
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D003433:Crosses, Genetic; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism; D048490:raf Kinases / Q000378:metabolism*
C489421:Bmi1 protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D025803:Tumor Suppressor Protein p14ARF; D063150:Polycomb Repressive Complex 1; D048490:raf Kinases