Gut Liver.  2017 Mar;11(2):261-269. 10.5009/gnl15389.

Establishment of Hepatocellular Cancer Induced Pluripotent Stem Cells Using a Reprogramming Technique

• Kim HJ
• Jeong J
• Park S
• Jin YW
• Lee SS
• Lee SB
• Choi D

• KMID: 2412193
• DOI: http://doi.org/10.5009/gnl15389

Abstract

BACKGROUND/AIMS
Cancer is known to be a disease by many factors. However, specific results of reprogramming by pluripotency-related transcription factors remain to be scarcely reported. Here, we verified potential effects of pluripotent-related genes in hepatocellular carcinoma cancer cells.
METHODS
To better understand reprogramming of cancer cells in different genetic backgrounds, we used four liver cancer cell lines representing different states of p53 (HepG2, Hep3B, Huh7 and PLC). Retroviral-mediated introduction of reprogramming related genes (KLF4, Oct4, Sox2, and Myc) was used to induce the expression of proteins related to a pluripotent status in liver cancer cells.
RESULTS
Hep3B cells (null p53) exhibited a higher efficiency of reprogramming in comparison to the other liver cancer cell lines. The reprogrammed Hep3B cells acquired similar characteristics to pluripotent stem cells. However, loss of stemness in Hep3B-iPCs was detected during continual passage.
CONCLUSIONS
We demonstrated that reprogramming was achieved in tumor cells through retroviral induction of genes associated with reprogramming. Interestingly, the reprogrammed pluripotent cancer cells (iPCs) were very different from original cancer cells in terms of colony shape and expressed markers. The induction of pluripotency of liver cancer cells correlated with the status of p53, suggesting that different expression level of p53 in cancer cells may affect their reprogramming.

Keyword

Liver neoplasms; Induced pluripotent stem cells; Reprogramming

MeSH Terms

Carcinoma, Hepatocellular/*genetics
Cell Line, Tumor
Cellular Reprogramming Techniques/*methods
Hep G2 Cells
Humans
Induced Pluripotent Stem Cells/*physiology
Kruppel-Like Transcription Factors/metabolism
Liver Neoplasms/*genetics
Octamer Transcription Factor-3/metabolism
Proto-Oncogene Proteins c-myc/metabolism
SOXB1 Transcription Factors/metabolism
Transcription Factors
Tumor Suppressor Protein p53/metabolism
Kruppel-Like Transcription Factors
Octamer Transcription Factor-3
Proto-Oncogene Proteins c-myc
SOXB1 Transcription Factors
Transcription Factors
Tumor Suppressor Protein p53