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

Becker M, Korn C, Sienerth AR, Voswinckel R, Luetkenhaus K, Ceteci F, Rapp UR - PLoS ONE (2009)

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Bayerisches Krebsforschungszentrum, University of Wuerzburg, Wuerzburg, Germany.

ABSTRACT

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.

Show MeSH

Related in: MedlinePlus

No evidence for BASCs in BXB lung tumors.Paraffin embedded lung sections from BXB11 mice were stained for pro SP-C (red) and for CC10 (green) to detect double positive bronchio alveolar stem cells (BASCs). A representative BASC cell that is located at a bronchio alveolar duct junction (BADJ) is indicated by white arrow. Scale bar = 30 µm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2626631&req=5

pone-0004230-g005: No evidence for BASCs in BXB lung tumors.Paraffin embedded lung sections from BXB11 mice were stained for pro SP-C (red) and for CC10 (green) to detect double positive bronchio alveolar stem cells (BASCs). A representative BASC cell that is located at a bronchio alveolar duct junction (BADJ) is indicated by white arrow. Scale bar = 30 µm.

Mentions: We next addressed the contribution of BASC cells to SP-C C-RAF BXB tumor formation. To this end we performed pro SP-C/CC10 double staining and analyzed BXB11 tumors for the presence of double positive cells. For this analysis image acquisition settings were chosen that allowed identification of BASCs at BADJs. As illustrated in Figure 5, no double positive cells could be observed in tumors.


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

Becker M, Korn C, Sienerth AR, Voswinckel R, Luetkenhaus K, Ceteci F, Rapp UR - PLoS ONE (2009)

No evidence for BASCs in BXB lung tumors.Paraffin embedded lung sections from BXB11 mice were stained for pro SP-C (red) and for CC10 (green) to detect double positive bronchio alveolar stem cells (BASCs). A representative BASC cell that is located at a bronchio alveolar duct junction (BADJ) is indicated by white arrow. Scale bar = 30 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2626631&req=5

pone-0004230-g005: No evidence for BASCs in BXB lung tumors.Paraffin embedded lung sections from BXB11 mice were stained for pro SP-C (red) and for CC10 (green) to detect double positive bronchio alveolar stem cells (BASCs). A representative BASC cell that is located at a bronchio alveolar duct junction (BADJ) is indicated by white arrow. Scale bar = 30 µm.
Mentions: We next addressed the contribution of BASC cells to SP-C C-RAF BXB tumor formation. To this end we performed pro SP-C/CC10 double staining and analyzed BXB11 tumors for the presence of double positive cells. For this analysis image acquisition settings were chosen that allowed identification of BASCs at BADJs. As illustrated in Figure 5, no double positive cells could be observed in tumors.

Bottom Line: 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.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).

View Article: PubMed Central - PubMed

Affiliation: Bayerisches Krebsforschungszentrum, University of Wuerzburg, Wuerzburg, Germany.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus