Browse

Oncogenic Ras-mediated downregulation of Clast1/LR8 is involved in Ras-mediated neoplastic transformation and tumorigenesis in NIH3T3 cells

Cited 5 time in Web of Science Cited 5 time in Scopus
Authors
Ryu, Sun-Hyo; Kim, Ki Hwan; Kim, Hong-Beum; Kim, Mi-Hwa; Kang, Yoonsung; Seo, Hong Joo; You, Ho Jin; Jun, Jae-Yeul; Hyun, Jin Won; Kim, Na-Hee
Issue Date
2010-09
Publisher
WILEY-BLACKWELL
Citation
CANCER SCIENCE; Vol.101 9; 1990-1996
Abstract
Oncogenic Ras proteins transform cells by way of multiple downstream signaling pathways that promote the genesis of human cancers. However, the exact cellular mechanisms by which downstream targets are regulated are not fully understood. Here, we show that oncogenic Ras reduced Clast1/LR8 transcript levels in mouse NIH3T3 fibroblasts and human WI38 fibroblasts. Clast1/LR8 transcript was undetectable in H460, A549, and H1299 cells showing high Ras activity, but was relatively abundant in DMS53 cells displaying low Ras activity. We also showed that K-Ras siRNA restored Clast1/LR8 expression in H460 and A549 cells, and that inhibitors of DNA methylation and histone deacetylation reversed oncogenic H-Ras-mediated suppression of Clast1/LR8 transcription. Additionally, ectopic expression of Clast1/LR8 inhibited serum-stimulated phosphorylation of ERK1/2 and Akt in H-RasV12-transformed NIH3T3 cells. We further showed that the expression of Clast1/LR8 interfered with oncogenic Ras-induced NIH3T3 cell transformation and invasion. Finally, our results showed that Clast1/LR8 inhibited Ras-induced proliferation of, and tumor formation by, oncogenic H-RasV12-transformed NIH3T3 cells in vivo. This study identifies the downregulation of Clast1/LR8 as a potentially important mechanism by which oncogenic Ras-mediated neoplastic transformation occurs. (Cancer Sci 2010).
ISSN
1347-9032
Language
English
URI
http://hdl.handle.net/10371/77619
DOI
https://doi.org/10.1111/j.1349-7006.2010.01626.x
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse