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Cited by 105

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Immortalization of Primary Human Prostate Epithelial Cells by c-Myc

Gil, Jesús, Kerai, Preeti, Lleonart, Matilde, Bernard, David, Cigudosa, Juan Cruz, Peters, Gordon, Carnero, Amancio, Beach, David·2005·Cancer Research
DOI 10.1158/0008-5472.can-03-4030

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Abstract

A significant percentage of prostate tumors have amplifications of the c-Myc gene, but the precise role of c-Myc in prostate cancer is not fully understood. Immortalization of human epithelial cells involves both inactivation of the Rb/p16INK4a pathway and telomere maintenance, and it has been recapitulated in culture by expression of the catalytic subunit of telomerase, hTERT, in combination with viral oncoproteins. Here, we show the immortalization of human prostate epithelial cells (HPrEC) by a single genetic event, the expression of the c-Myc oncogene. Myc stabilizes telomere length in HPrEC through up-regulation of hTERT expression and overrides the accumulation of cell cycle inhibitory proteins, such as p16INK4a. Overall, HPrECs expressing c-Myc retain many characteristics of normal cells, such as the induction of a senescence-like growth arrest in response to oncogenic Ras, an intact p53 response, and an absence of gross karyotypic abnormalities. However, HPrECs expressing c-Myc lack a Rb/p16INK4a checkpoint and can be transformed without the need for additional genetic lesions in that pathway. These results give a partial explanation for the physiologic role of c-Myc overexpression in prostate cancer.

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Cited by

Metadata

Authors
Gil, J., Kerai, P., Lleonart, M., Bernard, D., Cigudosa, J. C., Peters, G., Carnero, A., & Beach, D.
Affiliations
  • 1Molecular Oncology Laboratory, Cancer Research UK, London Research Institute;
  • 3University of Cambridge, Cancer Research UK, Department of Oncology and the Medical Research Council Cancer Cell Unit, Hutchinson/Medical Research Council Research Centre, Cambridge, United Kingdom;
  • 4Department of Pathology, Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Barcelona, Spain;
  • 5Free University of Brussels, Laboratory of Molecular Virology, Faculty of Medicine, Brussels, Belgium; and
  • 6Cytogenetics Unit, Biotechnology Program and
  • 7Experimental Therapeutics Program, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
  • 2Center for Cutaneous Biology, Institute for Cell and Molecular Sciences, London, United Kingdom;
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2005-03-15
Volume
65
Issue
6
Pages
2179-2185
ISSN
  • 0008-5472
  • 1538-7445
DOI
10.1158/0008-5472.can-03-4030
Cited by
105
References
12
Language
en
Update notices
correction (2022-07-18)

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