Journal ArticleDOI
Creation of human tumour cells with defined genetic elements
William C. Hahn,William C. Hahn,Christopher M. Counter,Ante S. Lundberg,Ante S. Lundberg,Roderick L. Beijersbergen,Mary W. Brooks,Robert A. Weinberg +7 more
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TLDR
It is shown that the ectopic expression of the telomerase catalytic subunit (hTERT) in combination with two oncogenes results in direct tumorigenic conversion of normal human epithelial and fibroblast cells.Abstract:
During malignant transformation, cancer cells acquire genetic mutations that override the normal mechanisms controlling cellular proliferation. Primary rodent cells are efficiently converted into tumorigenic cells by the coexpression of cooperating oncogenes1,2. However, similar experiments with human cells have consistently failed to yield tumorigenic transformants3,4,5, indicating a fundamental difference in the biology of human and rodent cells. The few reported successes in the creation of human tumour cells have depended on the use of chemical or physical agents to achieve immortalization6, the selection of rare, spontaneously arising immortalized cells7,8,9,10, or the use of an entire viral genome11. We show here that the ectopic expression of the telomerase catalytic subunit (hTERT)12 in combination with two oncogenes (the simian virus 40 large-T oncoprotein and an oncogenic allele of H-ras) results in direct tumorigenic conversion of normal human epithelial and fibroblast cells. These results demonstrate that disruption of the intracellular pathways regulated by large-T, oncogenic ras and telomerase suffices to create a human tumor cell.read more
Citations
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Journal ArticleDOI
The hallmarks of cancer.
TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
Journal ArticleDOI
Hepatocellular Carcinoma: Epidemiology and Molecular Carcinogenesis
TL;DR: A detailed understanding of epidemiologic factors and molecular mechanisms associated with HCC ultimately could improve current concepts for screening and treatment of this disease.
Journal ArticleDOI
Cellular senescence: when bad things happen to good cells
TL;DR: Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.
Journal ArticleDOI
Reprogramming of human somatic cells to pluripotency with defined factors
In-Hyun Park,In-Hyun Park,Rui Zhao,Rui Zhao,Jason A. West,Jason A. West,Akiko Yabuuchi,Akiko Yabuuchi,Hongguang Huo,Hongguang Huo,Tan A. Ince,Paul H. Lerou,M. William Lensch,M. William Lensch,George Q. Daley,George Q. Daley +15 more
TL;DR: The data demonstrate that defined factors can reprogramme human cells to pluripotency, and establish a method whereby patient-specific cells might be established in culture.
References
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Journal ArticleDOI
Specific association of human telomerase activity with immortal cells and cancer
Nam Woo Kim,Mieczyslaw A. Piatyszek,Karen R. Prowse,Calvin B. Harley,Michael D. West,Peter L. C. Ho,Gina M. Coviello,Woodring E. Wright,Scott L. Weinrich,Jerry W. Shay +9 more
TL;DR: A highly sensitive assay for measuring telomerase activity was developed in this paper, which showed that telomerases appear to be stringently repressed in normal human somatic tissues but reactivated in cancer, where immortal cells are likely required to maintain tumor growth.
Journal ArticleDOI
Extension of life-span by introduction of telomerase into normal human cells
Andrea G. Bodnar,Michel M. Ouellette,Maria Frolkis,Shawn E. Holt,Choy-Pik Chiu,Gregg B. Morin,Calvin B. Harley,Jerry W. Shay,Serge Lichtsteiner,Woodring E. Wright +9 more
TL;DR: In this article, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomere catalytic subunit.
Journal ArticleDOI
Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
Book ChapterDOI
Molecular genetic analysis of fission yeast Schizosaccharomyces pombe.
TL;DR: This chapter describes techniques concerned with classical and molecular genetics, cell biology, and biochemistry that can be used with Schizosaccharomyces pombe.
Journal ArticleDOI
A survey of telomerase activity in human cancer
Jerry W. Shay,Silvia Bacchetti +1 more
TL;DR: All major types of cancer have been screened and the presence of telomerase activity has been detected in the vast majority of cases, and a summary, in table form, of the current data is provided.