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10:03
Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
Creation of human tumour cells with defined genetic elements
W C Hahn1, C M Counter, A S Lundberg
1Department of Biology, Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, Cambridge 02142, USA.
Nature
|August 10, 1999
Summary
Creating human tumor cells is challenging. Scientists found that combining telomerase (hTERT) with two oncogenes directly converts normal human cells into tumorigenic cells, offering new insights into cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Malignant transformation involves genetic mutations overriding normal cell proliferation controls.
- Rodent cells transform readily with oncogenes, but human cells resist tumorigenic conversion.
- Previous human tumor cell creation required immortalization agents or viral genomes.
Purpose of the Study:
- To investigate a novel method for direct tumorigenic conversion of normal human cells.
- To determine if specific oncogenes and telomerase can induce human tumor formation.
- To elucidate the fundamental differences in human versus rodent cell transformation.
Main Methods:
- Ectopic expression of telomerase catalytic subunit (hTERT).
- Co-expression of simian virus 40 large-T oncoprotein and an oncogenic H-ras allele.
- Utilizing normal human epithelial and fibroblast cells.
Main Results:
- Direct tumorigenic conversion of human cells was achieved.
- The combination of hTERT, large-T oncoprotein, and oncogenic H-ras was effective.
- This approach bypasses the need for chemical/physical agents or spontaneous immortalization.
Conclusions:
- Disruption of pathways regulated by large-T, oncogenic ras, and telomerase is sufficient for human tumor cell creation.
- Highlights a key difference in human and rodent cell transformation mechanisms.
- Provides a new model for studying human tumorigenesis.
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