Nuclear hormone receptor NR4A2 is involved in cell transformation and apoptosis.
HeLaHF cells are transformation revertants of cervical cancer HeLa cells and have lost anchorage-independent growth potential and tumorigenicity. Activation of tumor suppressor(s) was implicated previously in this transformation reversion. In this study, expression profiling analysis was carried out to identify potential oncogenes that are down-regulated in HeLaHF cells. We found that all three members of the NR4A1/Nur77/NGFIB orphan nuclear hormone receptor subfamily (NR4A1, NR4A2, and NR4A3) were down-regulated in the HeLaHF revertant. Small interfering RNA-mediated down-regulation of NR4A2 in HeLa cells, either transiently or stably, resulted in reduced anchorage-independent growth that was largely attributable to increased anoikis. Furthermore, down-regulation of NR4A2 as well as NR4A1 promoted intrinsic apoptosis. These phenotypes were also observed in several other experimental cancer cells, suggesting the observed apoptosis suppression is a more general property of NR4A2 and NR4A1. These phenotypes also suggest that the Nur77/NGFIB subfamily of orphan receptors exhibit certain oncogenic functionalities with regards to cell proliferation and apoptosis and could therefore be evaluated as potential cancer therapeutic targets.
Ke
Ning
N
Immusol, Inc., San Diego, California 92121, USA.
Claassen
Gisela
G
Yu
De-Hua
DH
Albers
Aaron
A
Fan
Wufang
W
Tan
Philip
P
Grifman
Mirta
M
Hu
Xiuyuan
X
Defife
Kristin
K
Nguy
Vivian
V
Meyhack
Bernd
B
Brachat
Arndt
A
Wong-Staal
Flossie
F
Li
Qi-Xiang
QX
D017209:Apoptosis / Q000502:physiology*; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; C539882:NR4A2 protein, human; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D034741:RNA, Small Interfering; D014157:Transcription Factors