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

• Published in: Gut and liver 2017, 11(2), , pp.261-269
• Main Authors: Kim, Han Joon, Jeong, Jaemin, Park, Sunhoo, Jin, Young-Woo, Lee, Seung-Sook, Lee, Seung Bum, Choi, Dongho
• Format: Article
• Language: English
• Subjects: Carcinoma, Hepatocellular - genetics; Cell Line, Tumor; Cellular Reprogramming Techniques - methods; Hep G2 Cells; Humans; induced pluripotent stem cells; Induced Pluripotent Stem Cells - physiology; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors - metabolism; liver neoplasms; Liver Neoplasms - genetics; Octamer Transcription Factor-3 - metabolism; Original; Proto-Oncogene Proteins c-myc - metabolism; reprogramming; SOXB1 Transcription Factors - metabolism; Transcription Factors; Tumor Suppressor Protein p53 - metabolism; 내과학
• ISSN: 1976-2283; 2005-1212
• DOI: 10.5009/gnl15389

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. 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. 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. 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.