title: BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.
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.
authors.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.
authors.forename: Mehdi Hayat
authors.initials: MH
authors.lastname: Shahi
authors.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.
authors.forename: Daniel
authors.initials: D
authors.lastname: York
authors.affiliation: The Department of Pathology, Comprehensive Cancer Center, University of California Davis, Davis, California, United States of America.
authors.forename: Regina
authors.initials: R
authors.lastname: Gandour-Edwards
authors.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.
authors.forename: Sita S
authors.initials: SS
authors.lastname: Withers
authors.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.
authors.forename: Roseline
authors.initials: R
authors.lastname: Holt
authors.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.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Rebhun
mesh_terms: D000293:Adolescent; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006574:Heterocyclic Compounds, 2-Ring / Q000494:pharmacology; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006574:Heterocyclic Compounds, 2-Ring; C586999:PTC-209; D013844:Thiazoles; D004317:Doxorubicin; D016190:Carboplatin; D063150:Polycomb Repressive Complex 1