Asset Details
Do you wish to reserve the book?
Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways
Do you wish to request the book?
Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways
2017
Overview
MYC activation at modest levels has been frequently found in hepatocellular carcinoma. However, its significance in hepatocarcinogenesis has remained obscure. Here we examined the role of Myc activation in mouse liver tumours induced by hepatocytic expression of myristoylated
AKT
(
AKT
) and/or mutant
HRAS
V12
(
HRAS
) via transposon-mediated gene integration.
AKT
or
HRAS
alone required 5 months to induce liver tumours, whereas their combination generated hepatocellular carcinoma within 8 weeks. Co-introduction of
AKT
and
HRAS
induced lipid-laden preneoplastic cells that grew into nodules composed of tumour cells with or without intracytoplasmic lipid, with the latter being more proliferative and associated with spontaneous Myc expression.
AKT
/
HRAS
-induced tumorigenesis was almost completely abolished when MadMyc, a competitive Myc inhibitor, was expressed simultaneously. The Tet-On induction of MadMyc in preneoplastic cells significantly inhibited the progression of
AKT/HRAS
-induced tumours; its induction in transformed cells suppressed their proliferative activity with alterations in lipid metabolism and protein translation. Transposon-mediated Myc overexpression facilitated tumorigenesis by
AKT
or
HRAS
, and when it was co-introduced with
AKT
and
HRAS
, diffusely infiltrating tumours without lipid accumulation developed as early as 2 weeks. Examination of the dose-responses of
Myc
in the enhancement of
AKT/HRAS
-induced tumorigenesis revealed that a reduction to one-third retained enhancing effect but three-times greater introduction damped the process with increased apoptosis. Myc overexpression suppressed the mRNA expression of proteins involved in the synthesis of fatty acids, and when combined with
HRAS
introduction, it also suppressed the mRNA expression of proteins involved in their degradation. Finally, the MYC-positive human hepatocellular carcinoma was characterized by the cytoplasm devoid of lipid accumulation, prominent nucleoli and a higher proliferative activity. Our results demonstrate that in hepatocarcinogenesis induced by both activated AKT and HRAS, activation of endogenous Myc is an enhancing factor and adequate levels of Myc deregulation further facilitate the process with alterations in cellular metabolism.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/77
/ 45/44
/ 64/60
/ 82/58
/ 96/63
/ Animals
/ Carcinoma, Hepatocellular - genetics
/ Carcinoma, Hepatocellular - metabolism
/ Carcinoma, Hepatocellular - pathology
/ Cell Transformation, Neoplastic - genetics
/ Cell Transformation, Neoplastic - metabolism
/ Cell Transformation, Neoplastic - pathology
/ Cellular signal transduction
/ Humans
/ Lipids
/ Liver Neoplasms - metabolism
/ Male
/ Medicine
/ Mice
/ Nodules
/ Nucleoli
/ Oncology
/ Original
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Rodents
/ Tumors
