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2016 ; 7
(17
): 24284-302
Nephropedia Template TP
gab.com Text
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English Wikipedia
The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor
cell invasiveness and neuroendocrine differentiation in prostate cancer cells
#MMPMID27015368
Labrecque MP
; Takhar MK
; Nason R
; Santacruz S
; Tam KJ
; Massah S
; Haegert A
; Bell RH
; Altamirano-Dimas M
; Collins CC
; Lee FJ
; Prefontaine GG
; Cox ME
; Beischlag TV
Oncotarget
2016[Apr]; 7
(17
): 24284-302
PMID27015368
show ga
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, HIF1? 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 Rb plays in mediating
hypoxia-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 loss of Rb in conjunction
with hypoxia leads to aberrant expression of hypoxia-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.