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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 09, 2008 |
| Title |
Normal human prostate (NHP) epithelial cells: Senescent and immortalized cells compared to young progenitors |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Normal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo, but the underlying molecular mechanisms remain incompletely understood. Here we first show that multiple primary strains of NHP cells are all immunophenotyped as CK5+/CK18+CD44+α2β1+p63+hTERT+ progenitor cells, which gradually lose progenitor markers as they lose proliferative capacity. NHP cell senescence involves loss of telomerase expression, upregulation of p16, and activation of p53. Using genetically defined manipulations of these three signaling pathways, we show that p16 is the primary determinant of the NHP cell proliferative capacity and hTERT is required for unlimited proliferative lifespan. Hence, suppression of 16 alone significantly extends NHP cell lifespan but both p16 inhibition and hTERT are required to immortalize NHP cells. Importantly, the immortalized NHP cells are normal progenitors that possess the ability to differentiate into functional prostatic glands containing both basal and luminal cells and, frequently, neuroendocrine cells. The immortalized NHP cells possess gene expression profiles characteristic of proliferating progenitor cells. Our studies shed light on the molecular mechanisms regulating the proliferative lifespan of NHP progenitor cells and provide direct evidence that basal-like progenitor cells can regenerate the entire prostatic glands in vivo. The availability of these cells should facilitate future studies of prostate cancer development.
Further processed data linked below as Supplementary files.
TestvsControl: corresponding GSM#
3vs1: GSM266720, 721, 722
4vs1: GSM266727, 730, 731
5vs1: GSM266732, 733, 734
7avs1: GSM266735, 736, 737
9vs1: GSM266772, 773, 812
11vs1: GSM266813, 816, 823
13vs1: GSM266824, 826, 828
Note: The 'TestvsControl' comparisons report the top 100 up- or down-regulated genes. The numeric designations (1 to 13) are used in the corresponding manuscript. The 'SignificantGenes' lists were used in clustering analysis.
Keywords: Cell type comparison (senscent and immortalized NHP cells compared to young NHP progenitors)
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| Overall design |
Total 7 sets of two color arrays with 3 technical replicates in each set (total 21 individual arrays) were performed and each individual array included a test sample (experimental condition) and a control (young NHP progenitors) sample.
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| Contributor(s) |
Bhatia B, Jiang M, Patrawala L, Badeaux M, Schneider Broussard R, Multani A, Jeter CR, Suraneni MV, Calhoun Davis T, Hu L, Hu J, Tsavachidis S, Zhang W, Chang S, Hayward SW, Tang D |
| Citation(s) |
18662989 |
| Submission date |
Feb 19, 2008 |
| Last update date |
Feb 22, 2018 |
| Contact name |
Dean G Tang |
| E-mail(s) |
dtang@mdanderson.org
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| Organization name |
U.T M. D. Anderson Cancer Center
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| Department |
Carcinogenesis
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| Lab |
Dean G Tang's Lab
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| Street address |
1808 Park road 1C
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| City |
Smithville |
| State/province |
TX |
| ZIP/Postal code |
78957 |
| Country |
USA |
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| Platforms (1) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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| Samples (21)
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| GSM266720 |
NHP8 near senescent/senescent vs young_rep1 |
| GSM266721 |
NHP8 near senescent/senescent vs young_rep2 |
| GSM266722 |
NHP8 near senescent/senescent vs young_rep3 |
| GSM266727 |
NHP8/hTERT (Senescent) vs Young NHP8 cells_rep1 |
| GSM266730 |
NHP8/hTERT (Senescent) vs Young NHP8 cells_rep2 |
| GSM266731 |
NHP8/hTERT (Senescent) vs Young NHP8 cells_rep3 |
| GSM266732 |
NHP8/DNp53 (Senescent) vs Young NHP8 Cells_rep1 |
| GSM266733 |
NHP8/DNp53 (Senescent) vs Young NHP8 Cells_rep2 |
| GSM266734 |
NHP8/DNp53 (Senescent) vs Young NHP8 Cells_rep3 |
| GSM266735 |
NHP8/p16sh (near senescent) vs young NHP8 cells_rep1 |
| GSM266736 |
NHP8/p16sh (near senescent) vs young NHP8 cells_rep2 |
| GSM266737 |
NHP8/p16sh (near senescent) vs young NHP8 cells_rep3 |
| GSM266772 |
NHP8/p16sh+DNp53 (pre-senescent) vs young NHP8 cells_rep1 |
| GSM266773 |
NHP8/p16sh+DNp53 (pre-senescent) vs young NHP8 cells_rep2 |
| GSM266812 |
NHP8/p16sh+DNp53 (pre-senescent) vs young NHP8 cells_rep3 |
| GSM266813 |
NHP8/p16sh + hTERT (immortalized) vs young NHP8 cells_rep1 |
| GSM266816 |
NHP8/p16sh + hTERT (immortalized) vs young NHP8 cells_rep2 |
| GSM266823 |
NHP8/p16sh + hTERT (immortalized) vs young NHP8 cells_rep3 |
| GSM266824 |
NHP8/p16sh + hTERT + DNp53 (immortalized) vs young NHP8 cells_rep1 |
| GSM266826 |
NHP8/p16sh + hTERT + DNp53 (immortalized) vs young NHP8 cells_rep2 |
| GSM266828 |
NHP8/p16sh + hTERT + DNp53 (immortalized) vs young NHP8 cells_rep3 |
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| Relations |
| BioProject |
PRJNA107827 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10570_11vs1_top100_down.txt |
25.6 Kb |
(ftp)(http) |
TXT |
| GSE10570_11vs1_top100_up.txt |
24.9 Kb |
(ftp)(http) |
TXT |
| GSE10570_13vs1_top100_down.txt |
26.0 Kb |
(ftp)(http) |
TXT |
| GSE10570_13vs1_top100_up.txt |
25.7 Kb |
(ftp)(http) |
TXT |
| GSE10570_3vs1_top100_down.txt |
25.5 Kb |
(ftp)(http) |
TXT |
| GSE10570_3vs1_top100_up.txt |
25.9 Kb |
(ftp)(http) |
TXT |
| GSE10570_4vs1_top100_down.txt |
25.7 Kb |
(ftp)(http) |
TXT |
| GSE10570_4vs1_top100_up.txt |
25.8 Kb |
(ftp)(http) |
TXT |
| GSE10570_5vs1_top100_down.txt |
25.5 Kb |
(ftp)(http) |
TXT |
| GSE10570_5vs1_top100_up.txt |
25.8 Kb |
(ftp)(http) |
TXT |
| GSE10570_7avs1_top100_down.txt |
26.4 Kb |
(ftp)(http) |
TXT |
| GSE10570_7avs1_top100_up.txt |
25.8 Kb |
(ftp)(http) |
TXT |
| GSE10570_9vs1_top100_down.txt |
26.1 Kb |
(ftp)(http) |
TXT |
| GSE10570_9vs1_top100_up.txt |
26.2 Kb |
(ftp)(http) |
TXT |
| GSE10570_RAW.tar |
278.1 Mb |
(http)(custom) |
TAR (of TXT) |
| GSE10570_SignificantGenes_Intersection.txt |
1.1 Mb |
(ftp)(http) |
TXT |
| GSE10570_SignificantGenes_Union.txt |
9.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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