Schlafen 12 expression modulates prostate cancer cell differentiation.
Schlafen 12 expression modulates prostate cancer cell differentiation.
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DOI：
10.1016/j.jss.2014.03.069
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发表时间：
2014-07
影响因子：
2.2
通讯作者：
Basson, Marc D.
中科院分区：
文献类型：
--
作者：
Kovalenko, Pavlo L.;Basson, Marc D.
Schlafen 蛋白先前已被认为与白细胞和肠上皮分化有关。我们假设前列腺上皮细胞中 Schlafen 12 (SLFN12) 的过度表达会调节前列腺特异性抗原 (PSA) 和二肽基肽酶 4 (DPP4)（前列腺上皮分化标志物）的表达。在用编码 SLFN12-GFP (Ad-SLFN12) 或仅表达 GFP 的病毒（对照）的腺病毒载体感染后，比较前列腺癌细胞系 LNCaP 和 PC-3 的分化。通过 RT-PCR 评估 SLFN12、PSA 和 DPP4 的转录水平，并通过蛋白质印迹评估蛋白质水平。由于混合谱系激酶 (MLK) 及其下游效应器 (ERK) 之一先前已与前列腺上皮分化的某些方面有关，因此我们进行了进一步的研究，其中在 Ad-GFP-SLFN12 转染过程中将 LNCaP 细胞与 DMSO（对照）、PD98059（ERK 抑制剂）或 MLK 抑制剂共同处理 72 小时。与Ad-GFP处理的对照相比，用Ad-SLFN12处理LNCaP或PC-3细胞使PSA表达降低56.6±4.6% (p<0.05)，但使DPP4转录物水平增加4.8±1.0倍(p<0.05)。 LNCaP 细胞中的进一步研究表明，Ad-SLFN12 过表达增加了成熟 E-钙粘蛋白与其前体蛋白的比率。此外，当 MLK 或 ERK 被阻断时，SLFN12 过表达会促进 DPP4 表达。 ERK 抑制不能逆转 SLFN12 诱导的 PSA、E-钙粘蛋白或 DPP4 的变化。 SLFN12 可以调节前列腺上皮细胞的分化，至少部分独立于 ERK 或 MLK。了解 SLFN12 如何影响前列腺上皮分化可能最终确定影响前列腺恶性肿瘤表型的靶标。
Schlafen proteins have previously been linked to leukocyte and intestinal epithelial differentiation. We hypothesized that Schlafen 12 (SLFN12) overexpression in prostate epithelial cells would modulate expression of prostate-specific antigen (PSA) and dipeptidyl peptidase-4 (DPP4), markers of prostatic epithelial differentiation. Differentiation of the prostate cancer cell line LNCaP and PC-3 was compared after infection with an adenoviral vector coding for SLFN12-GFP (Ad-SLFN12) or GFP only expressing virus (control). Transcript levels of SLFN12, PSA and DPP4 were evaluated by RT-PCR and protein levels by Western blotting. Because Mixed Lineage Kinase (MLK) and one of its downstream effectors (ERK) have previously been implicated in some aspects of prostate epithelial differentiation, we conducted further studies in which LNCaP cells were co-treated with DMSO (control), PD98059 (ERK inhibitor) or MLK inhibitor during transfection with Ad-GFP-SLFN12 for 72 hours. Treatment of LNCaP or PC-3 cells with Ad-SLFN12 reduced PSA expression by 56.6±4.6% (p<0.05) but increased DPP4 transcript level by 4.8±1.0 fold (p<0.05) vs. Ad-GFP-treated controls. Further studies in LNCaP cells showed that Ad-SLFN12 overexpression increased the ratio of the mature E-cadherin protein to its precursor protein. Furthermore, SLFN12 overexpression promoted DPP4 expression either when MLK or ERK were blocked. ERK inhibition did not reverse SLFN12-induced changes in PSA, E-cadherin or DPP4. SLFN12 may regulate differentiation in prostate epithelial cells, at least in part independently of ERK or MLK. Understanding how SLFN12 influences prostatic epithelial differentiation may ultimately identify targets to influence the phenotype of prostatic malignancy.
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影响因子：
4.4
作者：
Kovalenko, Pavlo L.;Zhang, Zhentao;Fleet, James C.
通讯作者：
Fleet, James C.
影响因子：
6
作者：
Massoner, Petra;Rennau, Michael Ladurner;Klocker, Helmut
通讯作者：
Klocker, Helmut
影响因子：
3.7
作者：
Laurenzana A;Balliu M;Cellai C;Romanelli MN;Paoletti F
通讯作者：
Paoletti F
影响因子：
2.2
作者：
Kovalenko, Pavlo L.;Basson, Marc D.
通讯作者：
Basson, Marc D.
DOI：
10.1016/j.bbrc.2008.03.032
发表时间：
2008-05-23
影响因子：
3.1
作者：
Neumann, Brent;Zhao, Liang;Gonda, Thomas J.
通讯作者：
Gonda, Thomas J.