Circadian clock gene expression regulates cancer cell growth through glutaminase

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...

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Published inActa biochimica et biophysica Sinica Vol. 46; no. 5; pp. 409 - 414
Main Authors Huang, Aixia, Bao, Bingbo, Gaskins, H Rex, Liu, Haijun, Zhang, Xueli, Lu, Liwen, Gao, Shan, Shi, Yihai, Zhang, Ming, Shan, Yuanzhou, Feng, Jing, Yao, Guoxiang
Format Journal Article
LanguageEnglish
Published China Oxford University Press 01.05.2014
Subjects
Animals
Base Sequence
Cell Division
Circadian Clocks - genetics
DNA Primers
Gene Expression Regulation, Neoplastic
Glutaminase - genetics
Glutaminase - metabolism
Male
Mice
Mice, Inbred BALB C
Real-Time Polymerase Chain Reaction
基因表达
恶性肿瘤细胞
昼夜节律钟
生物钟基因
细胞生长
聚合酶链反应
肝癌
谷氨酰胺酶
glutaminase
circadian clock gene
cancer
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Summary: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 （Bmall） 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.
Bibliography: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 （Bmall） 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.
31-1940/Q
circadian clock gene; glutaminase; cancer
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1672-9145
1745-7270
1745-7270
DOI:10.1093/abbs/gmu012