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Epistatic interaction between the lipase-encoding genes and causes liposarcoma in mice


Liposarcoma is an often fatal adult-onset tumor of fat tissue. Lipolysis, the central pathway of fat tissue metabolism, has been implicated in cancer. We generated mice that were deficient in two key enzymes of lipolysis, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). Strikingly, all mice with combined ATGL and HSL deficiency developed liposarcoma by 11–14 months of age. No liposarcoma occurred in single knockout or normal controls. Transcriptome analysis revealed that a subset of genes is dysregulated by 3 months of age. Our study reveals a novel epistatic interaction in fat cells between these two lipase genes and that causes a unique form of liposarcoma in mice. The double knockout mice provide a novel tool to study the early stages of liposarcoma development, prognostic markers and preventive treatments.


Vyšlo v časopise: Epistatic interaction between the lipase-encoding genes and causes liposarcoma in mice. PLoS Genet 13(5): e32767. doi:10.1371/journal.pgen.1006716
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1006716

Souhrn

Liposarcoma is an often fatal adult-onset tumor of fat tissue. Lipolysis, the central pathway of fat tissue metabolism, has been implicated in cancer. We generated mice that were deficient in two key enzymes of lipolysis, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL). Strikingly, all mice with combined ATGL and HSL deficiency developed liposarcoma by 11–14 months of age. No liposarcoma occurred in single knockout or normal controls. Transcriptome analysis revealed that a subset of genes is dysregulated by 3 months of age. Our study reveals a novel epistatic interaction in fat cells between these two lipase genes and that causes a unique form of liposarcoma in mice. The double knockout mice provide a novel tool to study the early stages of liposarcoma development, prognostic markers and preventive treatments.


Zdroje

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