title: The effect of Zhangfei on the unfolded protein response and growth of cells derived from canine and human osteosarcomas.
abstract: The objective of this study was to determine whether the protein Zhangfei could suppress the unfolded protein response (UPR) and growth of osteosarcoma cells. Dog (D-17) and a human (Saos-2) osteosarcoma cells were infected with adenovirus vectors expressing either Zhangfei or the control protein beta- galactosidase. We monitored cell growth as well as levels of UPR gene transcripts and proteins. We found that Zhangfei suppressed the growth of both D-17 and Saos-2 cells. Zhangfei-expressing D-17 cells displayed large vacuoles containing culture medium and expressed phosphatidylserine on their external surface suggesting that Zhangfei induced macropinocytosis and apoptosis in these cells. While Zhangfei inhibited the growth of both D-17 and Saos-2 cells, it inhibited thapsigargin-induced UPR, as detected by a decrease in transcripts for UPR genes, and HERP and GRP78 proteins, only in D-17 cells, suggesting that the ability of Zhangfei to suppress the UPR and tumour cells growth may not be linked.
authors.affiliation: Department of Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Bergeron
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Elliot
authors.forename: N
authors.initials: N
authors.lastname: Rapin
authors.forename: V
authors.initials: V
authors.lastname: MacDonald
authors.forename: K
authors.initials: K
authors.lastname: Linn
authors.forename: E
authors.initials: E
authors.lastname: Simko
authors.forename: V
authors.initials: V
authors.lastname: Misra
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004285:Dogs; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism*; D017510:Protein Folding; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C411104:CREBZF protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human