Proteomic analysis and molecular characterization of tissue ferritin light chain in hepatocellular carcinoma

Kang Sik Park, Hoguen Kim, Nam Gyun Kim, Sang Yun Cho, Kun Ho Choi, Je Kyung Seong, Young Ki Paik

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111 Citations (Scopus)

Abstract

To investigate a molecular basis for iron depletion in human hepatocellular carcinoma (HCC), 19 cases of HCC were analyzed by two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Results were compared with those of paired adjacent nontumorous liver tissues. Comparative analysis of the respective spot patterns in 2DE showed that tissue ferritin light chain (T-FLC), an iron-storage protein, was either severely suppressed or reduced to undetectable levels in HCC, which was further supported by Western blot and immunohistochemical analysis. In contrast, transferrin receptor (TfR) was shown to be overexpressed in the same HCC samples. Interestingly, the relative levels of messenger RNA (mRNA) expression of T-FLC in HCC, which were measured by a real-time quantitative reverse-transcription polymerase chain reaction (PCR), exhibited almost the same levels as those in normal tissues, suggesting that the translational or posttranslational modification of T-FLC may be the cause of T-FLC suppression in HCC. Furthermore, with PCR-based loss of heterozygosity analysis, only 1 of 19 HCCs showed chromosomal deletions at 19q13.3-q13.4 where T-FLC is located, indicating that the suppression of T-FLC is unlikely due to structural genomic changes with HCC. In conclusion, both proteomic and genomic evidence support not only a basis for the suppression of T-FLC in HCC but also provide a new clue to the unresolved question of iron depletion during hepatocarcinogenesis.

Original languageEnglish
Pages (from-to)1459-1466
Number of pages8
JournalHepatology
Volume35
Issue number6
DOIs
Publication statusPublished - 2002 Jun

Bibliographical note

Funding Information:
Abbreviations: HCC, hepatocellular carcinoma; SF, serum ferritin; TF, tissue ferritin; T-FLC, tissue ferritin light chain; T-FHC, tissue ferritin heavy chain; 2DE, two-dimensional gel electrophoresis; MALDI-MS, matrix-assisted laser desorption ionization mass spectrometry; PCR, polymerase chain reaction; TfR, transferrin receptor; mRNA, messenger RNA; IRP, iron regulatory protein. From the 1Yonsei Proteome Research Center, Department of Biochemistry and Bioproducts Research Center, Yonsei University; and 2Department of Pathology and 3Medical Research Center, Yonsei University Medical School, Seoul, Korea. Received August 15, 2001; accepted February 27, 2002. Supported by the grant “21C Frontier Project: Functional Genomics of the Human Genome” (to Y.-K.P., FG-1-4-01). Address reprint requests to: Young-Ki Paik, Ph.D., Yonsei Proteome Research Center, S309 Kwahakwon, Yonsei University, 134 Shinchon-dong Sudaemoon-ku, Seoul, 120-749, Korea. E-mail: paikyk@yonsei.ac.kr; fax: (82) 2-393-6589. Copyright © 2002 by the American Association for the Study of Liver Diseases. 0270-9139/02/3506-0020$35.00/0 doi:10.1053/jhep.2002.33204

All Science Journal Classification (ASJC) codes

  • Hepatology

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