Establishment and characterization of a cancer cell line derived from an aggressive childhood liver tumor

Tina T.L. Chen, Dinesh Rakheja, Jaclyn Y. Hung, Peter J. Hornsby, Piotr Tabaczewski, Marcio Malogolowkin, James Feusner, Frank Miskevich, Roger Schultz, Gail E. Tomlinson

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21 Scopus citations

Abstract

Background. Hepatoblastoma is a rare malignancy of childhood. The scarcity of adequate cell models has limited our understanding of this tumor. Here we describe and characterize a new human liver tumor cell line, Hep293TT, derived from an aggressive childhood hepatoblastoma. Procedures. Hep293TT cells were established using primary tumor tissues from a 5-year-old Caucasian female child. This cell line has been maintained for more than 34 months and over 20 subcultures, and was characterized by histopathology, ELISA, genotype, cytogenetics, CGH array, immunohistochemistry, and molecular sequence analyses. Results. Cells were confirmed to originate from parental tumor cells, secrete α-fetoprotein, and express hepatic markers and β-catenin. Hep293TT cells were able to form colonies in soft agar. Tumorigenicity was demonstrated by induction of solid tumors after subrenal capsule injection in immunodeficient mice. Hep293TT cells demonstrated a highly aneuploid karyotype, and a whole genome CGH analysis revealed chromosomal imbalances in every chromosome. Allelotype analysis demonstrated loss of alleles at distal 11p15.5 as is typical of embryonal tumors. Both Hep293TT cells and the primary tumor contain a deletion of 351 nucleotides in β-catenin, as has been seen in other hepatoblastoma tumors. The cell line expressed β-catenin protein in both full-length and partially deleted forms, and expressed NOTCH2 protein characteristic of hepatoblasts. No mutation was detected in the APC, MYH, MLH1, or MSH2 genes. Conclusion. This cell line, Hep293TT, is a valuable resource for the study of childhood liver cancer and may potentially provide a tool in the development of new agents.

Original languageEnglish (US)
Pages (from-to)1040-1047
Number of pages8
JournalPediatric Blood and Cancer
Volume53
Issue number6
DOIs
StatePublished - Dec 8 2009

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Keywords

  • Alpha-fetoprotein
  • Childhood hepatoblastoma
  • NOTCH2
  • Transitional liver cell tumor
  • β-catenin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Chen, T. T. L., Rakheja, D., Hung, J. Y., Hornsby, P. J., Tabaczewski, P., Malogolowkin, M., Feusner, J., Miskevich, F., Schultz, R., & Tomlinson, G. E. (2009). Establishment and characterization of a cancer cell line derived from an aggressive childhood liver tumor. Pediatric Blood and Cancer, 53(6), 1040-1047. https://doi.org/10.1002/pbc.22187