![](http://investorshub.advfn.com/images/default_ih_profile2_4848.jpg?cb=0)
Wednesday, August 23, 2006 10:10:18 AM
Original Article
Oncogene (2006) 25, 5037–5045. doi:10.1038/sj.onc.1209513; published online 17 April 2006
Expression of hTERT immortalises normal human urothelial cells without inactivation of the p16/Rb pathway
E J Chapman1, C D Hurst1, E Pitt1, P Chambers2, J S Aveyard1 and M A Knowles1
1Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, UK
2Cancer Research UK Mutation Detection Facility, St James's University Hospital, Leeds, UK
Correspondence: Dr MA Knowles, Cancer Research UK Clinical Centre, St James's University Hospital, Beckett Street, Leeds LS97TF, UK. E-mail: margaret.knowles@cancer.org.uk
Received 23 June 2005; Revised 7 February 2006; Accepted 15 February 2006; Published online 17 April 2006.
Top of pageAbstract
The CDKN2A locus is frequently inactivated in urothelial cell carcinoma (UCC), yet how this alteration contributes to bladder tumorigenesis is not known. Although most UCC express telomerase, inactivation of the p16/Rb pathway is generally required for in vitro immortalisation. This and the involvement of p16 in senescence of normal human urothelial cells (NHUC) suggest that CDKN2A deletion may aid bypass of senescence and allow immortalisation. CDKN2A encodes p16 and p14ARF and therefore inactivation of this locus can disrupt both the Rb and p53 tumour suppressor pathways. Retrovirus-mediated transduction was used to specifically modulate the p16/Rb and/or p53 tumour suppressor pathways in NHUC and to express human telomerase reverse transcriptase (hTERT). Expression of hTERT bypassed Rb and p53 pathway-dependent barriers to proliferation and immortalised NHUC. TERT-NHUC had normal karyotypes, were non-tumorigenic and unexpectedly retained CDKN2A. Thus, the phenotypic significance of inactivation of CDKN2A in UCC may not be solely related to bypass of senescence. Phenotypic assays in human urothelial cells have relied on cell strains derived from invasive tumours or NHUC immortalised by expression of SV40-large T. The production of genetically normal but immortal NHUC lines now provides a valuable platform for experiments to examine the timing and combination of events necessary for UCC tumorigenesis.
Recent GERN News
- Geron Corporation Reports Second Quarter 2024 Financial Results and Business Highlights • Business Wire • 08/08/2024 11:00:00 AM
- Geron Announces Updated NCCN Guidelines® Recommending RYTELO™ (imetelstat) for the Treatment of Symptomatic Anemia in Patients with Lower-Risk MDS • Business Wire • 07/26/2024 11:30:00 AM
- Geron Corporation Announces Chief Commercial Officer to Depart at End of August 2024 • Business Wire • 07/23/2024 08:15:00 PM
- Geron to Announce Second Quarter 2024 Financial Results on August 8, 2024 • Business Wire • 07/18/2024 08:30:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 07/10/2024 08:05:04 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 07/08/2024 07:44:18 PM
- Geron Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) • Business Wire • 06/20/2024 08:30:00 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/12/2024 08:05:08 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/12/2024 08:05:04 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/10/2024 09:53:19 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/10/2024 04:30:13 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:08 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:06 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:05 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:03 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/07/2024 08:10:03 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 06/07/2024 08:03:44 PM
- Geron Announces FDA Approval of RYTELO™ (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia • Business Wire • 06/07/2024 01:58:00 AM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 06/05/2024 08:05:20 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 06/04/2024 09:02:18 PM
- Form 4 - Statement of changes in beneficial ownership of securities • Edgar (US Regulatory) • 05/17/2024 08:05:30 PM
- Geron Reports Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) • Business Wire • 05/16/2024 08:30:00 PM
- Form 144 - Report of proposed sale of securities • Edgar (US Regulatory) • 05/15/2024 08:07:34 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 05/13/2024 08:05:15 PM
HealthLynked Corp. Announces Second Quarter and First Half 2024 Results: Continued Cost Reductions Set the Stage for Strategic Shift to App-Based Technology Services • HLYK • Aug 16, 2024 8:00 AM
PickleJar Announces Official Name Change and New Ticker Symbol • NREG • Aug 15, 2024 2:23 PM
VAYK's Q2 Profit Added to Accumulated Net Profit of Over $2.2 Million In 18 Months • VAYK • Aug 15, 2024 9:07 AM
Swifty Global Reports Strong Q2 Performance and Prepares for Major Exchange Uplisting • DRCR • Aug 15, 2024 9:04 AM
Mayback's Global Entertainment Signs Global Distribution Agreement with Children's Media Studio • AHRO • Aug 15, 2024 8:45 AM
POET Technologies Reports Second Quarter 2024 Financial Results • POET • Aug 15, 2024 8:04 AM