title: Circadian clock gene expression regulates cancer cell growth through glutaminase.
abstract: Glutamine is an essential amino acid for malignant tumor cells. Glutaminase that metabolizes glutamine reaches a maximum expression in tumors immediately before the maximum proliferation rate. Tumor cells grow at different rates during the day. We postulated that the activity of glutaminase in tumor cells is subject to the regulation of circadian clock gene. We measured glutaminase by western blot analysis and circadian clock gene expression by real-time polymerase chain reaction in the liver and tumor cells at six equispaced time points of the day in individual mice of a 12/12 h light/dark schedule. The results showed that the tumor-bearing mice, under normal diurnal conditions, are circadianly entrained, as reflected by the normal host locomotor activity rhythms and rhythmic liver clock gene expression. The tumors within these mice are also circadianly organized, as reflected by circadian clock gene (Bmal1) expression. What is most remarkable is that kidney-type glutaminase also showed circadian rhythms in the same pattern with tumor circadian clock gene expression in liver cancer xenograft model, indicating that conditionally inhibiting glutaminase activity may provide a new target for cancer therapy.
authors.affiliation: Department of Medicine, South Campus, Shanghai Jiaotong University 6th Hospital, Shanghai 201499, China.
authors.forename: Aixia
authors.initials: A
authors.lastname: Huang
authors.forename: Bingbo
authors.initials: B
authors.lastname: Bao
authors.forename: H Rex
authors.initials: HR
authors.lastname: Gaskins
authors.forename: Haijun
authors.initials: H
authors.lastname: Liu
authors.forename: Xueli
authors.initials: X
authors.lastname: Zhang
authors.forename: Liwen
authors.initials: L
authors.lastname: Lu
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Yihai
authors.initials: Y
authors.lastname: Shi
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Yuanzhou
authors.initials: Y
authors.lastname: Shan
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Yao
mesh_terms: D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D057906:Circadian Clocks / Q000235:genetics*; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D005972:Glutaminase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D005972:Glutaminase
keywords: cancer; circadian clock gene; glutaminase