N-myc downstream-regulated gene 1/Cap43 may function as tumor suppressor in endometrial cancer.
OBJECTIVE
N-myc downstream-regulated gene 1 (NDRG1) reportedly regulates tumor progression in various cancers. Our previous studies showed that NDRG1 was aberrantly overexpressed in human endometrial cancer tissues. The purpose of the present study was to investigate the role of NDRG1 in endometrial carcinogenesis.


METHODS
A short hairpin RNA (shRNA)-mediated gene silencing strategy was employed to stably suppress the expression of NDRG1 in endometrial cancer Ishikawa cells. The influence of NDRG1 silencing on cancer cell biological behaviors was examined through observing in vitro tumor cell proliferation, colony formation, cell migration and invasion. Moreover, the mammalian NDRG1 expression vector pcDNA3.1(+)/NDRG1 was constructed to determine the effects of NDRG1 overexpression on cell proliferation and migration. Additionally, gene expression microarray analysis was conducted to identify NDRG1 downstream target genes after NDRG1 knockdown.


RESULTS
It was demonstrated that NDRG1 knockdown significantly enhanced Ishikawa cell proliferation and dramatically promoted cell migration and invasion. Furthermore, overexpression of NDRG1 in Ishikawa cells greatly inhibited cell proliferation and migration. Through microarray analysis and data mining, a large cohort of NDRG1-repressed target genes were identified. Additionally, through comparing the current microarray results with those obtained previously in studies of cervical and ovarian cancer cells conducted by us, 19 more specific common downstream target genes were identified.


CONCLUSIONS
It was demonstrated that NDRG1 might carry out a tumor suppressor function during endometrial carcinogenesis. The identification of downstream target genes should afford meaningful hints for prospective investigations. The tumor suppressor function of NDRG1 may open a new window for the target therapy of endometrial cancer.
Department of Pathology, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, NO.85, Wujin Road, Shanghai 200080, People's Republic of China.
Xiu-Hong
XH
Lv
Jia-Wei
JW
Chen
Gang
G
Zhao
Zhen-Zhong
ZZ
Feng
Dao-Hua
DH
Yang
Wei-Wei
WW
Sun
Jin-Shuang
JS
Fan
Guang-Hui
GH
Zhu
D018797:Cell Cycle Proteins / Q000235:genetics*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques / Q000379:methods; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D000099259:N-myc Downstream-Regulated Gene 1 Protein
D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein