TY - JOUR
T1 - RelB enhances prostate cancer growth
T2 - Implications for the role of the nuclear factor-κb alternative pathway in tumorigenicity
AU - Xu, Yong
AU - Josson, Sajni
AU - Fang, Fang
AU - Oberley, Terry D.
AU - Clair, Daret K.St
AU - Wan, X. Steven
AU - Sun, Yulan
AU - Bakthavatchalu, Vasudevan
AU - Muthuswamy, Anantharaman
AU - Clair, William H.St
PY - 2009/4/15
Y1 - 2009/4/15
N2 - The nuclear faetor-κB (NP-κB) classic pathway is thought to be critical for tumorigenesis, but little is known about the role of the NF-κB alternative pathway in cancer development. Recently, high constitutive nuclear levels of RelB have been observed in human prostate cancer specimens with high Gleason scores. Here, we used four complementary approaches to test whether RelB contributes to tumorigenicity of prostate cancer. Inhibiting RelB in aggressive androgenindependent PC-3 cells by stable or conditional expression of a dominant-negative p100 mutant significantly reduced the incidence and growth rate of tumors. The decrease in tumorigenicity coincided with a reduction in the NF-κB target interleukin-8 (IL-8). Consistently, down-regulation of RelB by small interfering RNA targeting also reduced tumor growth and decreased levels of IL-8. Conversely, stable expression of RelB in androgen-responsive LNCaP tumors increased the circulating IL-8 levels. Taken together, these results reveal a tumor-supportive role of RelB, implicate the NF-κB alternative pathway as a potential target for preventing prostate cancer, and suggest the use of IL-8 as a marker for prostate cancer prognosis.
AB - The nuclear faetor-κB (NP-κB) classic pathway is thought to be critical for tumorigenesis, but little is known about the role of the NF-κB alternative pathway in cancer development. Recently, high constitutive nuclear levels of RelB have been observed in human prostate cancer specimens with high Gleason scores. Here, we used four complementary approaches to test whether RelB contributes to tumorigenicity of prostate cancer. Inhibiting RelB in aggressive androgenindependent PC-3 cells by stable or conditional expression of a dominant-negative p100 mutant significantly reduced the incidence and growth rate of tumors. The decrease in tumorigenicity coincided with a reduction in the NF-κB target interleukin-8 (IL-8). Consistently, down-regulation of RelB by small interfering RNA targeting also reduced tumor growth and decreased levels of IL-8. Conversely, stable expression of RelB in androgen-responsive LNCaP tumors increased the circulating IL-8 levels. Taken together, these results reveal a tumor-supportive role of RelB, implicate the NF-κB alternative pathway as a potential target for preventing prostate cancer, and suggest the use of IL-8 as a marker for prostate cancer prognosis.
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U2 - 10.1158/0008-5472.CAN-08-4635
DO - 10.1158/0008-5472.CAN-08-4635
M3 - Article
C2 - 19351823
AN - SCOPUS:65949109942
SN - 0008-5472
VL - 69
SP - 3267
EP - 3271
JO - Cancer Research
JF - Cancer Research
IS - 8
ER -