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| Status |
Public on Feb 24, 2016 |
| Title |
The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role of Rb in HIF1-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that Rb regulates specific chromosomal gene clusters and loss of Rb in conjunction with hypoxia leads to dysregulation of HIF1-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies.
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| Overall design |
RNAs derived from human LNCaP cells stably infected with either scrambled control shRNA or a shRNA directed to RB1. Cells were exposed to either 24 h hypoxia (1% O2) or maintained under normoxic conditions. Biological triplicates were tested and compared.
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| Contributor(s) |
Beischlag TV, Cox ME |
| Citation(s) |
27015368 |
| Submission date |
Feb 24, 2016 |
| Last update date |
Oct 02, 2019 |
| Contact name |
Shawn Anderson |
| E-mail(s) |
Sanderson@prostatecentre.com
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| Organization name |
Vancouver Prostate Centre
|
| Lab |
Laboratory for Advanced Genome Analysis
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| Street address |
2660 Oak Street
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V6H3Z6 |
| Country |
Canada |
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| Platforms (1) |
| GPL13497 |
Agilent-026652 Whole Human Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA313019 |
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