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Expression of HNFs and C/EBP alpha is correlated with immunocytochemical differentiation of cell lines derived from human hepatocellular carcinomas, hepatoblastomas and immortalized hepatocytes.
Cancer Sci. 2003 Sep; 94(9):757-63.CS

Abstract

Objective assessment of the differentiation grade of hepatocellular carcinomas (HCCs) is important for evaluation of the pathological diagnosis, prognosis and therapeutic treatment. Differentiation of hepatocytes is reflected by their expression of hepatic functional proteins in the mouse embryo, and liver-enriched transcription factors (LETFs) have been shown to regulate hepatic functional genes strictly. Previous reports demonstrated that the level of LETF expression is altered in HCC or preneoplastic nodules compared with noncancerous tissues. Therefore, LETF expression levels might be useful as a measure of HCC maturation. In this study, to clarify the correlation between the expression of LETFs and the differentiation grade of HCCs, we performed a quantitative analysis of the mRNA expressions of HNFs and C/EBP alpha using real-time reverse-transcription PCR and immunocytochemical analysis for hepatic functional proteins in twelve cell lines. Furthermore, we examined orthotopic transplantations of the HCC cell lines in C.B-17/Icrj-scid/scid mice and characterized the histologic and cytologic differentiation of the tumors that developed. Our results showed that comprehensive expressions of HNF-3beta, HNF-4 alpha, HNF-1 alpha, and C/EBP alpha were specific to HCCs with well-differentiated function and morphology. Furthermore, among these four transcription factors, HNF-4 alpha and HNF-1 alpha expressions showed synchronism and had a close relation with HCC differentiation. These in vitro results were confirmed in tumors developed in SCID mice in vivo. These findings suggested that HNF-4 alpha and HNF-1 alpha are useful markers to assess the degree of HCC differentiation, which we suggest could be evaluated objectively by the quantitative analysis of HNFs and C/EBP alpha in HCCs.

Authors+Show Affiliations

Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki-shi, Ibaraki 305-8575, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12967472

Citation

Ishiyama, Tadashi, et al. "Expression of HNFs and C/EBP Alpha Is Correlated With Immunocytochemical Differentiation of Cell Lines Derived From Human Hepatocellular Carcinomas, Hepatoblastomas and Immortalized Hepatocytes." Cancer Science, vol. 94, no. 9, 2003, pp. 757-63.
Ishiyama T, Kano J, Minami Y, et al. Expression of HNFs and C/EBP alpha is correlated with immunocytochemical differentiation of cell lines derived from human hepatocellular carcinomas, hepatoblastomas and immortalized hepatocytes. Cancer Sci. 2003;94(9):757-63.
Ishiyama, T., Kano, J., Minami, Y., Iijima, T., Morishita, Y., & Noguchi, M. (2003). Expression of HNFs and C/EBP alpha is correlated with immunocytochemical differentiation of cell lines derived from human hepatocellular carcinomas, hepatoblastomas and immortalized hepatocytes. Cancer Science, 94(9), 757-63.
Ishiyama T, et al. Expression of HNFs and C/EBP Alpha Is Correlated With Immunocytochemical Differentiation of Cell Lines Derived From Human Hepatocellular Carcinomas, Hepatoblastomas and Immortalized Hepatocytes. Cancer Sci. 2003;94(9):757-63. PubMed PMID: 12967472.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of HNFs and C/EBP alpha is correlated with immunocytochemical differentiation of cell lines derived from human hepatocellular carcinomas, hepatoblastomas and immortalized hepatocytes. AU - Ishiyama,Tadashi, AU - Kano,Junko, AU - Minami,Yuko, AU - Iijima,Tatsuo, AU - Morishita,Yukio, AU - Noguchi,Masayuki, PY - 2003/9/12/pubmed PY - 2004/2/18/medline PY - 2003/9/12/entrez SP - 757 EP - 63 JF - Cancer science JO - Cancer Sci VL - 94 IS - 9 N2 - Objective assessment of the differentiation grade of hepatocellular carcinomas (HCCs) is important for evaluation of the pathological diagnosis, prognosis and therapeutic treatment. Differentiation of hepatocytes is reflected by their expression of hepatic functional proteins in the mouse embryo, and liver-enriched transcription factors (LETFs) have been shown to regulate hepatic functional genes strictly. Previous reports demonstrated that the level of LETF expression is altered in HCC or preneoplastic nodules compared with noncancerous tissues. Therefore, LETF expression levels might be useful as a measure of HCC maturation. In this study, to clarify the correlation between the expression of LETFs and the differentiation grade of HCCs, we performed a quantitative analysis of the mRNA expressions of HNFs and C/EBP alpha using real-time reverse-transcription PCR and immunocytochemical analysis for hepatic functional proteins in twelve cell lines. Furthermore, we examined orthotopic transplantations of the HCC cell lines in C.B-17/Icrj-scid/scid mice and characterized the histologic and cytologic differentiation of the tumors that developed. Our results showed that comprehensive expressions of HNF-3beta, HNF-4 alpha, HNF-1 alpha, and C/EBP alpha were specific to HCCs with well-differentiated function and morphology. Furthermore, among these four transcription factors, HNF-4 alpha and HNF-1 alpha expressions showed synchronism and had a close relation with HCC differentiation. These in vitro results were confirmed in tumors developed in SCID mice in vivo. These findings suggested that HNF-4 alpha and HNF-1 alpha are useful markers to assess the degree of HCC differentiation, which we suggest could be evaluated objectively by the quantitative analysis of HNFs and C/EBP alpha in HCCs. SN - 1347-9032 UR - https://www.unboundmedicine.com/medline/citation/12967472/Expression_of_HNFs_and_C/EBP_alpha_is_correlated_with_immunocytochemical_differentiation_of_cell_lines_derived_from_human_hepatocellular_carcinomas_hepatoblastomas_and_immortalized_hepatocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=1347-9032&date=2003&volume=94&issue=9&spage=757 DB - PRIME DP - Unbound Medicine ER -