A homeobox protein, prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma.
OBJECTIVE
It has been shown that a lymphatic differentiation master gene, prox1, also plays an essential role in fetal hepatocyte migration. Its expression is detected in embryonic hepatoblasts and in adult hepatocytes. Hepatoma cells are similar to embryonic hepatoblasts to a certain extent because they both proliferate and invade the surrounding tissue. To address the possibility that Prox1 may be involved in the tumorigenesis of hepatocellular carcinoma (HCC), human clinical samples were analyzed.


METHODS
To screen prox1 as a potential tumor suppressor gene, its expression was analyzed in HCC cell lines and in human HCC tissues. Its growth-conferring abilities were assessed by transiently overexpressing Prox1 in HCC cell lines and by knocking down its expression by RNA interference.


RESULTS
We found that there was a significant correlation between Prox1 expression and the differentiation scores of the tumors. Subsequently, we also showed that low expression of Prox1 in tumors was closely associated with a poor prognosis. The specific knockdown of Prox1 by RNA interference strongly accelerated in vitro cell growth, whereas the overexpression of Prox1 greatly suppressed the growth.


CONCLUSIONS
Our results suggest that Prox1 is involved in the differentiation and progression of HCC, and thus it may be a candidate for the development of novel diagnostic and therapeutic strategies for HCC.
Shimoda
Masayuki
M
Molecular and Cancer Research Unit, HMRO, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takahashi
Meiko
M
Yoshimoto
Takanobu
T
Kono
Tomoya
T
Ikai
Iwao
I
Kubo
Hajime
H
D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D009362:Neoplasm Metastasis; D011379:Prognosis; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
D017931:DNA Primers; D018398:Homeodomain Proteins; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein