Transforming Growth Factor‐α Induces the Differentiation of Sarcomatoid Cholangiocarcinoma Cells

Enjoji, Munechika; Nakashima, Mitsuyoshi; Nakamuta, Makoto; Nawata, Hajime

doi:10.1111/j.1349-7006.2000.tb00935.x

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…We have also con®rmed that ETK-1 can also differentiate along a biliary epithelial lineage after transforming growth factor-(TGF) stimulation, although the percentage ef®ciency of transformation is lower than in the case with 5-azaCR treatment. 22 From these ®ndings, we consider that the differentiation stage of ETK-1 is consistent with liver stem cells. Figure lA).…”

Section: Resultsmentioning

confidence: 96%

“…We believe that this is because TGF causes only a low rate of transformation and because the transformed cells have a much lower proliferative capacity than original ETK-1. 22 Then we examined the SSP-25 and RBE cell lines, which are of identical origin but at different maturation stages, as a model for differentiation along a biliary epithelial lineage (group 2, Table 1, Figure 1B). In these CC cell lines, the telomerase activity of RBE (an adenocarcinoma cell line) was about 70% of that of SSP-25 (a sarcomatoid cell line); that is to say, its activity was signi®cantly reduced in the more mature stage.…”

Section: Resultsmentioning

confidence: 99%

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Telomerase activity is repressed during differentiation along the hepatocytic and biliary epithelial lineages: verification on immortal cell lines from the same origin

Fukutomi

Enjoji

Iguchi

et al. 2001

Cell Biochemistry & Function

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Recent investigations indicate that telomerase activity regulates the life span of cells by compensating for telomere shortening during DNA replication. In addition, as differentiation progresses, telomerase activity is reduced in several different cell lineages. These findings lend support to the theory that more immature cells have greater remaining proliferative capacity and longer life span. However, it has not been directly demonstrated that the differentiation along a hepatocytic or a bile ductal lineage is accompanied by reduction of telomerase activity. In this study, we present direct evidence that telomerase activity is reduced during hepatocytic and biliary epithelial differentiation by using our unique cell lines including a stem-like cell line, ETK-1. When hepatocytic differentiation was induced in ETK-1 by 5-azacytidine, telomerase activity decreased significantly. Similarly, when we compared the telomerase activity on SSP-25 and RBE cell lines from the same origin but representing different maturation stages of cholangiocarcinoma, more mature cells were found to possess significantly lower activity. These results indicate that the generally accepted relationship between telomerase activity and differentiation stage also applies in the hepatocytic and biliary epithelial lineages.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

Telomerase activity is repressed during differentiation along the hepatocytic and biliary epithelial lineages: verification on immortal cell lines from the same origin

Fukutomi

Enjoji

Iguchi

et al. 2001

Cell Biochemistry & Function

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“…We previously studied RCAS1 expression in established cell lines, 29,35 namely, the cholangiocarcinoma (CC) cell lines 40–45 ETK‐1, NEC, SSP‐25, RBE, and H‐1, and hepatocellular carcinoma (HCC) cell lines MEK, 41,42 PLC/PRF/5, and HepG2. RCAS1 mRNA was quantified by real‐time reverse transcription polymerase chain reaction (Fig.…”

Section: Immunohistochemical Rcas1 Expression In Carcinomasmentioning

confidence: 99%

Significance of RCAS1 antigen in hepatocellular, cholangiocellular and pancreatic carcinomas

Enjoji

Nakashima

Yamaguchi

et al. 2005

J of Gastro and Hepatol

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Since receptor-binding cancer antigen expressed on SiSo cells (RCAS1) was first reported as a tumorassociated antigen of gynecologic cancer, its function and practical value as a tumor marker have been investigated in various types of carcinomas. Basic research has indicated that RCAS1 expression in cancer cells contributes to the evasion from immune surveillance and progression of carcinomas. The clinical significance of RCAS1 expression in hepatobiliary and pancreatic carcinomas has also been investigated. In this review, we summarize the clinical application of RCAS1 antigen in hepatic and pancreaticobiliary diseases. We present new data and review current knowledge about the potential of RCAS1 as a tumor marker and the relationship between RCAS1 expression and clinicopathologic parameters. We found that the clinical function of RCAS1 appeared to differ according to the type of carcinoma. In hepatocellular carcinoma, the clinical significance of histological RCAS1 expression was controversial and that of serum RCAS1 levels showed little clinical value. In pancreaticobiliary cancers, high RCAS1 expression in tissue samples was an unfavorable independent prognostic factor. Serum RCAS1 was a superior tumor marker reflecting the disease activity in biliary carcinoma. In pancreatic cancer, serum RCAS1 levels were less useful than in biliary carcinoma but may be available for genetically CA19-9-negative patients and for CA19-9-non-producing cancer. This review also offers suggestions for future studies.

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Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor

et al. 2003

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Transforming Growth Factor‐α Induces the Differentiation of Sarcomatoid Cholangiocarcinoma Cells

Abstract: Our data suggest that TGFα α α α can act as a differentiation factor along a biliary epithelial lineage.

Cited by 4 publications

References 33 publications

Telomerase activity is repressed during differentiation along the hepatocytic and biliary epithelial lineages: verification on immortal cell lines from the same origin

Telomerase activity is repressed during differentiation along the hepatocytic and biliary epithelial lineages: verification on immortal cell lines from the same origin

Significance of RCAS1 antigen in hepatocellular, cholangiocellular and pancreatic carcinomas

Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor

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