Page 92 - D. Cancer biology

[D. Cancer biology-60]

Downregulation of TMEM176B protein is promotes

Oncogenic-Ras activated tumor progression

HONG BEUM KIM¹

¹Department of Premedical Course, Chosun University School of Medicine, Gwangju 61452, Republic of Korea

The neoplastic transformation by mutant RAS is thought to require remodeling of expression of an entire set of
genes. However, the mechanism underlying Ras-activated tumor metastasis remains unclear. Here we show that
oncogenic Ras decreases TMEM176B transcript production in mouse fibroblast NIH3T3 cells. TMEM176B transcript

was undetectable in H460, A549, and H1299 cells exhibiting high Ras activity, but was relatively abundant in DMS53

cells containing low Ras activity. Furthermore, we demonstrate that TMEM176B transcription downregulated by
oncogenic H-Ras. The ectopic expression of TMEM176B inhibited the epidermal growth factor (EGF)-stimulated
ERK1/2 phosphorylation in H-RasV12-transformed NIH3T3 cells. Finally, our results show that TMEM176B inhibits

Ras-induced cell proliferation and tumor formation by oncogenic H-RasV12-transformed NIH3T3 cells. This study
identifies the downregulation of TMEM176B as a potentially important mechanism by which oncogenic Ras-

mediated.