| Evidence that senescent human prostate epithelial cells enhance tumorigenicity: cell fusion as a potential mechanism and inhibition by p16INK4a and hTERT. | |
| | |
MedLine Citation:
|
PMID: 18059027 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo but the potential role of senescent NHP cells in prostate tumorigenesis remain unclear. Here we show that senescent NHP cells enhance the in vivo tumorigenicity of low-tumorigenic LNCaP prostate cancer and low/non-tumorigenic subset of cells (called L cells) isolated from multiple bulk-cultured prostate (and other) cancer cell lines. Subsequent studies suggest cell-cell fusion as a potential mechanism for senescent NHP cell-enhanced tumor development. Using fluorescently tagged tumor cells and/or NHP cells, we find that NHP cells, like fibroblasts, can undergo fusion with unfractionated tumor cells or the L cells. Using 293T-L cells as the model cell system, we verify NHP and 293T-L cell fusion by using differential RT-PCR, karyotyping, and gene expression analyses. Further experiments demonstrate that senescent NHP cells that have lost progenitor markers, accumulated p16INK4a (p16) protein expression, and acquired the AR mRNA expression, appear to be the preferential fusion targets. Strikingly, the tumorigenicity of the NHP/293T-L hybrid cells was inhibited by exogenous p16 as well as hTERT. Chromosomal analyses revealed that hTERT probably inhibited the in vivo tumorigenicity by maintaining genomic stability. These results suggest that senescent NHP cells, like senescent fibroblasts, may promote tumor development and that one of the mechanisms underlying the senescent NHP cell-enhanced tumorigenicity could be through cell fusion. |
| | |
Authors:
|
Bobby Bhatia; Asha S Multani; Lubna Patrawala; Xin Chen; Tammy Calhoun-Davis; Jianjun Zhou; Lisa Schroeder; Robin Schneider-Broussard; Jianjun Shen; Sen Pathak; Sandy Chang; Dean G Tang |
Related Documents
:
|
11748027 - A biologically based model of growth and senescence of syrian hamster embryo (she) cell... 12890857 - Mouse and human cells versus oxygen. 9117557 - Pyramidal nerve cell loss in alzheimer's disease. 1940337 - Inhibition by brefeldin a of the specific b cell antigen presentation to mhc class ii-r... 19906117 - Vitamin d - a new treatment for airway remodelling in asthma? 19725107 - The niche of stellate cells within rat liver. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
|
Title: International journal of cancer. Journal international du cancer Volume: 122 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2008 Apr |
Date Detail:
|
Created Date: 2008-02-04 Completed Date: 2008-02-26 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
|
Languages: eng Pagination: 1483-95 Citation Subset: IM |
Copyright Information:
|
(c) 2007 Wiley-Liss, Inc. |
Affiliation:
|
Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Aging* Cell Fusion* Cell Transformation, Neoplastic Cyclin-Dependent Kinase Inhibitor p16 / metabolism* Epithelial Cells / metabolism, pathology* Humans Karyotyping Male Mutation Polymorphism, Single-Stranded Conformational Prostate / metabolism*, pathology* Prostatic Neoplasms / etiology, metabolism, pathology* Telomerase / metabolism* Tumor Suppressor Protein p53 / genetics |
| Grant Support | |
ID/Acronym/Agency:
|
AG023374/AG/NIA NIH HHS; ES015888/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cyclin-Dependent Kinase Inhibitor p16; 0/Tumor Suppressor Protein p53; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Growth retardation and destruction of experimental squamous cell carcinoma by interstitial radioacti...
Next Document: Invasive breast cancer cells exhibit increased mobility of the actin-binding protein CapG.