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BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.

Shahi MH, York D, Gandour-Edwards R, Withers SS, Holt R, Rebhun RB - PLoS ONE (2015)

Bottom Line: BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA).Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined.An identical staining pattern was found in both primary and metastatic human OSA tissues.

View Article: PubMed Central - PubMed

Affiliation: The Comparative Oncology Laboratory and Center for Companion Animal Health, School of Veterinary Medicine, University of California Davis, Davis, CA, 95616, United States of America.

ABSTRACT
BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.

No MeSH data available.


Related in: MedlinePlus

Effect of PTC-209 on BMI1 and p16 protein expression in canine OSA cell lines.Western blot showing decreased BMI1 protein expression and increased p16 protein expression in Abrams, D17, and Moresco canine OSA cell lines after 24hrs (BMI1) and 48hrs (p16) of PTC-209 treatment. Protein band densities were calculated for each sample, values were normalized to actin, and then shown as a percent change in expression relative to vehicle control.
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pone.0131006.g007: Effect of PTC-209 on BMI1 and p16 protein expression in canine OSA cell lines.Western blot showing decreased BMI1 protein expression and increased p16 protein expression in Abrams, D17, and Moresco canine OSA cell lines after 24hrs (BMI1) and 48hrs (p16) of PTC-209 treatment. Protein band densities were calculated for each sample, values were normalized to actin, and then shown as a percent change in expression relative to vehicle control.

Mentions: Canine OSA cell lines were treated with PTC-209 (100, 200, or 500nM) for 24hrs and BMI1 expression was analyzed in a western blot assay (Fig 7). Compared to vehicle control, BMI1 protein expression decreased by 40% and 25% in the Abrams and D17 cell lines, respectively, following 500nM PTC-209 treatment. In the Moresco cell line, BMI1 protein expression decreased by 16% and 39% following 200nM and 500nM PTC-209 treatment, respectively, as compared to vehicle control. To assess changes in p16 protein expression, canine OSA cell lines were treated with similar doses of PTC-209 for 48hrs and analyzed with western blot (Fig 7). Increases in p16 protein levels could be observed in all cell lines beginning at 100nM PTC-209 and were highest at the 500nM PTC-209 dose for Abrams (120% increase) and Moresco (200% increase), but appeared to top out at 200nM for the D17 cell line (54% increase).


BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.

Shahi MH, York D, Gandour-Edwards R, Withers SS, Holt R, Rebhun RB - PLoS ONE (2015)

Effect of PTC-209 on BMI1 and p16 protein expression in canine OSA cell lines.Western blot showing decreased BMI1 protein expression and increased p16 protein expression in Abrams, D17, and Moresco canine OSA cell lines after 24hrs (BMI1) and 48hrs (p16) of PTC-209 treatment. Protein band densities were calculated for each sample, values were normalized to actin, and then shown as a percent change in expression relative to vehicle control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482432&req=5

pone.0131006.g007: Effect of PTC-209 on BMI1 and p16 protein expression in canine OSA cell lines.Western blot showing decreased BMI1 protein expression and increased p16 protein expression in Abrams, D17, and Moresco canine OSA cell lines after 24hrs (BMI1) and 48hrs (p16) of PTC-209 treatment. Protein band densities were calculated for each sample, values were normalized to actin, and then shown as a percent change in expression relative to vehicle control.
Mentions: Canine OSA cell lines were treated with PTC-209 (100, 200, or 500nM) for 24hrs and BMI1 expression was analyzed in a western blot assay (Fig 7). Compared to vehicle control, BMI1 protein expression decreased by 40% and 25% in the Abrams and D17 cell lines, respectively, following 500nM PTC-209 treatment. In the Moresco cell line, BMI1 protein expression decreased by 16% and 39% following 200nM and 500nM PTC-209 treatment, respectively, as compared to vehicle control. To assess changes in p16 protein expression, canine OSA cell lines were treated with similar doses of PTC-209 for 48hrs and analyzed with western blot (Fig 7). Increases in p16 protein levels could be observed in all cell lines beginning at 100nM PTC-209 and were highest at the 500nM PTC-209 dose for Abrams (120% increase) and Moresco (200% increase), but appeared to top out at 200nM for the D17 cell line (54% increase).

Bottom Line: BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA).Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined.An identical staining pattern was found in both primary and metastatic human OSA tissues.

View Article: PubMed Central - PubMed

Affiliation: The Comparative Oncology Laboratory and Center for Companion Animal Health, School of Veterinary Medicine, University of California Davis, Davis, CA, 95616, United States of America.

ABSTRACT
BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.

No MeSH data available.


Related in: MedlinePlus