Artemin stimulates oncogenicity and invasiveness of human endometrial carcinoma cells.
Here, we provide evidence for a functional role of artemin (ARTN) in progression of endometrial carcinoma (EC). Increased ARTN protein expression was observed in EC compared with normal endometrial tissue, and ARTN protein expression in EC was significantly associated with higher tumor grade and invasiveness. Forced expression of ARTN in EC cells significantly increased total cell number as a result of enhanced cell cycle progression and cell survival. In addition, forced expression of ARTN significantly enhanced anchorage-independent growth and invasiveness of EC cells. Moreover, forced expression of ARTN increased tumor size in xenograft models and produced highly proliferative, poorly differentiated, and invasive tumors. The ARTN-stimulated increases in oncogenicity and invasion were mediated by increased expression and activity of AKT1. Small interfering RNA-mediated depletion or antibody inhibition of ARTN significantly reduced oncogenicity and invasion of EC cells. Thus, inhibition of ARTN may be considered as a potential therapeutic strategy to retard progression of EC.
Pandey
Vijay
V
The Liggins Institute, University of Auckland, 2-6 Park Avenue, Private Bag 92019 Auckland, New Zealand.
Qian
Peng-Xu
PX
Kang
Jian
J
Perry
Jo K
JK
Mitchell
Murray D
MD
Yin
Zhinan
Z
Wu
Zheng-Sheng
ZS
Liu
Dong-Xu
DX
Zhu
Tao
T
Lobie
Peter E
PE
D000818:Animals; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009215:Myometrium / Q000473:pathology; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010641:Phenotype
C490886:ARTN protein, human; D009419:Nerve Tissue Proteins