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Target Protein for Xklp2 Functions as Coactivator of Androgen Receptor and Promotes the Proliferation of Prostate Carcinoma Cells.
Sun B
,
Long Y
,
Xiao L
,
Wang J
,
Yi Q
,
Tong D
,
Li K
.
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The activation of the androgen receptor (AR) pathway is crucial in the progression of human prostate cancer. Results of the present study indicated that the target protein xenopus kinesin-like protein (TPX2) enhanced the transcription activation of AR and promoted the proliferation of LNCaP (ligand-dependent prostate carcinoma) cells. The protein-protein interaction between AR and TPX2 was investigated using coimmunoprecipitation assays. Results of the present study further demonstrated that TPX2 enhanced the transcription factor activation of AR and enhanced the expression levels of the downstream gene prostate-specific antigen (PSA). TPX2 did this by promoting the accumulation of AR in the nucleus and also promoting the recruitment of AR to the androgen response element, located in the promoter region of the PSA gene. Overexpression of TPX2 enhanced both the in vitro and in vivo proliferation of LNCaP cells. By revealing a novel role of TPX2 in the AR signaling pathway, the present study indicated that TPX2 may be an activator of AR and thus exhibits potential as a novel target for prostate carcinoma treatment.
Figure 1. TPX2 enhanced the transcription factor activation of AR in LNCaP cells. LNCaP cells were cotransfected with empty vector, TPX2, or siTPX2 with luciferase reporters (ARE-Luc or PSA-Luc) and harvested for luciferase experiments. The activation of ARE-Luc (a) or PSA-Luc (b) was shown as mean ± SD. P < 0.05.
Figure 2. TPX2 enhanced the mRNA or protein expression of AR's down gene PSA in LNCaP cells. LNCaP cells were transfected with plasmids (control, TPX2, or siTPX2). Then, cells were harvested for qPXR or Western blot experiments. The mRNA level of PSA was examined by qPCR and shown as mean ± SD (a). The protein level of PSA or TPX2 was examined by Western blot, and the results were shown as the images of Western blot (b) or the quantitative results of the images (c–e). ∗P < 0.05.
Figure 3. TPX2 interacted with AR in LNCaP cells. LNCaP cells were transfected with FLAG, FLAG-TOX2 (a) or FLAG, FLAG-AR (b) and harvested for the IP assays. The results were shown as images of Western blot.
Figure 4. TPX2 enhanced the recruitment of AR to the PSA's promoter region or the accumulation of AR in nucleus. LNCaP cells were transfected with plasmids. The recruitment of AR to PSA's promoter was examined by ChIP (a). The accumulation of AR in nucleus was examined by the subcellular fraction (b and c). The results were shown as the images or the quantitative results. ∗P < 0.05.
Figure 5. The clinical significance of the TPX2-AR axis. (a and b) The mRNA level of TPX2 (a) or PSA (b) in prostate carcinoma or nontumor specimens was examined by qPCR. (c and d) The relationship between the expression of TPX2 with PSA was shown as scatter plot images. ∗P < 0.05.
Figure 6. TPX2 enhanced the in vitro proliferation of LNCaP cells. LNCaP cells were transfected with plasmids and analyzed by the colony formation. The results were shown as the images of colonies (a) or the quantitative results of colony images (b). The expression level of PSA or AR in LNCaP cells was examined by Western blot (c). ∗P < 0.05.
Figure 7. TPX2 enhanced the in vitro proliferation of LNCaP cells. LNCaP cells were transfected with plasmids and injected into the nude mice to form subcutaneous tumors. The results were shown as the images of tumor tissues (a), or the quantitative results of tumors according to the tumor volumes (c), or tumor weights (d). The expression level of PSA or AR in tumor tissues was examined by Western blot (b). ∗P < 0.05.
Figure 8. Schematic of TPX2 roles in prostate cancer progression. TPX2 enhanced the transcription factor activation of AR (a), inhibiting TPX2 is a potential therapeutic target against prostate cancer progression via AR signaling suppression (b).
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