Identification of a secretory protein c19orf10 activated in hepatocellular carcinoma.
The identification of genes involved in tumor growth is crucial for the development of inventive anticancer treatments. Here, we have cloned a 17-kDa secretory protein encoded by c19orf10 from hepatocellular carcinoma (HCC) serial analysis of gene expression libraries. Gene expression analysis indicated that c19orf10 was overexpressed in approximately two-thirds of HCC tissues compared to the adjacent noncancerous liver tissues, and its expression was significantly positively correlated with that of alpha-fetoprotein (AFP). Overexpression of c19orf10 enhanced cell proliferation of AFP-negative HLE cells, whereas knockdown of c19orf10 inhibited cell proliferation of AFP-positive Hep3B and HuH7 cells along with G1 cell cycle arrest. Supplementation of recombinant c19orf10 protein in culture media enhanced cell proliferation in HLE cells, and this effect was abolished by the addition of antibodies developed against c19orf10. Intriguingly, c19orf10 could regulate cell proliferation through the activation of Akt/mitogen-activated protein kinase pathways. Taken together, these data suggest that c19orf10 might be one of the growth factors and potential molecular targets activated in HCC.
Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Ishikawa, Japan.
Hajime
H
Sunagozaka
Masao
M
Honda
Taro
T
Yamashita
Ryuhei
R
Nishino
Hajime
H
Takatori
Kuniaki
K
Arai
Tatsuya
T
Yamashita
Yoshio
Y
Sakai
Shuichi
S
Kaneko
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
D007378:Interleukins; C464565:MYDGF protein, human; D000509:alpha-Fetoproteins