Long interspersed nucleotide acid element-1 ORF-1 protein promotes proliferation and invasion of human colorectal cancer LoVo cells through enhancing ETS-1 activity.
The human proto-oncogene long interspersed nucleotide acid element-1 (LINE-1) open reading frame-1 protein (ORF-1p) is involved in the progress of several cancers. The transcription factor ETS-1 can mediate the transcription of some downstream genes that play specific roles in the regulation of cancerous cell invasion and metastasis. In this study, the effects of LINE-1 ORF-1p on ETS-1 activity and on the proliferation and invasion of human colorectal cancer LoVo cells were investigated. Results showed that the overexpression of LINE-1 ORF-1p enhanced the transcription of ETS-1 downstream genes and increased their protein levels, and downregulation of the LINE-1 ORF-1p level by small interfering RNA (siRNA) reduced the transcriptional activation of ETS-1. In addition, overexpression of LINE-1 ORF-1p promoted LoVo cell proliferation and anchor-independent growth, and a knockdown of the LINE-1 protein level by siRNA reduced the proliferation and anchor-independent growth ability of LoVo cells. In vivo data revealed that LINE-1 ORF-1p overexpression increased LoVo tumor growth in nude mice, whereas the siRNA knockdown of endogenous LINE-1 ORF-1p expression decreased LoVo cell growth in nude mice. Therefore, LINE- 1 ORF-1p could promote LoVo cell proliferation and invasion both in vitro and in vivo, indicating that it might be a useful molecular target for the treatment of human colorectal cancer.
Department of Gastroenterology, Nan Lou Division, Chinese PLA General Hospital, Beijing, China.
M Y
MY
Li
Department of Gastroenterology, Nan Lou Division, Chinese PLA General Hospital, Beijing, China.
M
M
Zhu
Department of Pharmacy, General Hospital of Shenyang Military Command, Shenyang, China.
F
F
Feng
Department of Gastroenterology, Nan Lou Division, Chinese PLA General Hospital, Beijing, China.
F Y
FY
Cai
Department of Gastroenterology, Nan Lou Division, Chinese PLA General Hospital, Beijing, China.
K C
KC
Fan
Department of Gastroenterology, Nan Lou Division, Chinese PLA General Hospital, Beijing, China.
H
H
Jiang
Department of Gastroenterology, Nan Lou Division, Chinese PLA General Hospital, Beijing, China zhiqiangwangcn@163.com.
Z Q
ZQ
Wang
Department of Gastroenterology, Nan Lou Division, Chinese PLA General Hospital, Beijing, China.
E Q
EQ
Linghu
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D061986:MCF-7 Cells; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D016366:Open Reading Frames / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D000077022:Survivin; D015533:Transcriptional Activation / Q000235:genetics; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C107489:BIRC5 protein, human; C494041:ETS1 protein, human; D051034:Inhibitor of Apoptosis Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D000077022:Survivin; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1