Defined factors induce reprogramming of gastrointestinal cancer cells

Although cancer is a disease with genetic and epigenetic origins, the possible effects of reprogramming by defined factors remain to be fully understood. We studied the effects of the induction or inhibition of cancer-related genes and immature status-related genes whose alterations have been report...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 2010-01, Vol.107 (1), p.40-45
Hauptverfasser: Miyoshi, Norikatsu, Ishii, Hideshi, Nagai, Ken-ichi, Hoshino, Hiromitsu, Mimori, Koshi, Tanaka, Fumiaki, Nagano, Hiroaki, Sekimoto, Mitsugu, Doki, Yuichiro, Mori, Masaki
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container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 107
creator Miyoshi, Norikatsu
Ishii, Hideshi
Nagai, Ken-ichi
Hoshino, Hiromitsu
Mimori, Koshi
Tanaka, Fumiaki
Nagano, Hiroaki
Sekimoto, Mitsugu
Doki, Yuichiro
Mori, Masaki
description Although cancer is a disease with genetic and epigenetic origins, the possible effects of reprogramming by defined factors remain to be fully understood. We studied the effects of the induction or inhibition of cancer-related genes and immature status-related genes whose alterations have been reported in gastrointestinal cancer cells. Retroviral-mediated introduction of induced pluripotent stem (iPS) cell genes was necessary for inducing the expression of immature status-related proteins, including Nanog, Ssea4, Tra-1-60, and Tra-1-80 in esophageal, stomach, colorectal, liver, pancreatic, and cholangiocellular cancer cells. Induced cells, but not parental cells, possessed the potential to express morphological patterns of ectoderm, mesoderm, and endoderm, which was supported by epigenetic studies, indicating methylation of DNA strands and the histone H3 protein at lysine 4 in promoter regions of pluripotency-associated genes such as NANOG. In in vitro analysis induced cells showed slow proliferation and were sensitized to differentiation-inducing treatment, and in vivo tumorigenesis was reduced in NOD/SCID mice. This study demonstrated that pluripotency was manifested in induced cells, and that the induced pluripotent cancer (iPC) cells were distinct from natural cancer cells with regard to their sensitivity to differentiation-inducing treatment. Retroviral-mediated introduction of iPC cells confers higher sensitivity to chemotherapeutic agents and differentiation-inducing treatment.
doi_str_mv 10.1073/pnas.0912407107
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subjects Adipocytes
Animals
Antineoplastic Agents - pharmacology
Biological Sciences
Biomarkers - metabolism
Cancer
Cell Differentiation - drug effects
Cell Differentiation - physiology
Cell Line, Tumor
Cell lines
Cells
Cellular differentiation
Deoxyribonucleic acid
DNA
DNA (Cytosine-5-)-Methyltransferases - genetics
DNA (Cytosine-5-)-Methyltransferases - metabolism
DNA Methylation
DNA Methyltransferase 3A
DNA Methyltransferase 3B
Embryonic stem cells
Epigenesis, Genetic
Epithelial cells
Eye Proteins - genetics
Eye Proteins - metabolism
Gastrointestinal Neoplasms - genetics
Gastrointestinal Neoplasms - metabolism
Gastrointestinal Neoplasms - pathology
Gene expression
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Induced pluripotent stem cells
Lentivirus - genetics
Mice
Mice, Inbred NOD
Mice, SCID
Nanog Homeobox Protein
Neoplastic Stem Cells - cytology
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - physiology
Neurons
Octamer Transcription Factor-3 - genetics
Octamer Transcription Factor-3 - metabolism
Paired Box Transcription Factors - genetics
Paired Box Transcription Factors - metabolism
PAX6 Transcription Factor
Pluripotent stem cells
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - drug effects
Pluripotent Stem Cells - physiology
Proteins
Repressor Proteins - genetics
Repressor Proteins - metabolism
Retroviridae - genetics
Rodents
SOXB1 Transcription Factors - genetics
SOXB1 Transcription Factors - metabolism
Stem cells
title Defined factors induce reprogramming of gastrointestinal cancer cells
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