However, multiple lines of evidence shows that TLR4 expression is increased in prostate tissues from prostate cancer patients, and altered TLR4 signals may promote cancer development, as well as antitumor effects.
RESULTS The results revealed that TLR4 and COX-2 were upregulated in PCa tissues; Silencing of TLR4 or COX-2 inhibited PCa cell proliferation, migration, and invasion, and TLR4 siRNAs combined with COX-2 siRNAs synergistically suppressed PCa cell proliferation, migration, and invasion.
To understand the molecular mechanisms involved in TLR4 mediated PCa survival, we next investigated change in expression of markers for apoptosis, senescence and autophagy.
Although not statistically significant, TLR4 variation appeared to influence the association between T. vaginalis serostatus and prostate cancer risk consistent with the hypothesis that inflammation plays a role in this association.
Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality.
The combined findings of the current study and our previous study suggest that Prx1 interaction with TLR4 promotes CaP growth potentially through chronic activation of tumor angiogenesis.
In a mouse prostate cancer model, administration with the plasmid construct expressing siRNA for TLR4 obviously inhibited established tumor growth and survival.
Homozygosity for the variant alleles of eight SNPs was associated with a statistically significantly lower risk of prostate cancer (TLR4_1893, TLR4_2032, TLR4_2437, TLR4_7764, TLR4_11912, TLR4_16649, TLR4_17050, and TLR4_17923), but the TLR4_15844 polymorphism corresponding to 11381G/C was not associated with prostate cancer (GG versus CG/CC: OR, 1.01; 95% confidence interval, 0.79-1.29).
Our previous finding of an association of TLR4 gene sequence variants and prostate cancer risk provides evidence for a role of TLRs in prostate cancer.