The Potential Tumor-Suppressor DHRS7 Inversely Correlates with EGFR Expression in Prostate Cancer Cells and Tumor Samples.
The Potential Tumor-Suppressor DHRS7 Inversely Correlates with EGFR Expression in Prostate Cancer Cells and Tumor Samples.
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潜在的肿瘤抑制剂DHRS7与前列腺癌细胞和肿瘤样品中的EGFR表达成反比。
作者：
前列腺癌是男性最常见的恶性肿瘤之一。目前的疗法最初是有效的，但往往会产生耐药性，导致肿瘤复发和死亡。需要进一步研究新的参与者，参与前列腺癌的机制和治疗抗性。我们使用蛋白质组和基因表达分析研究了DHRS 7在前列腺癌细胞中的作用，DHRS 7是一种潜在的肿瘤抑制因子，目前其生理功能尚不清楚。尽管DHRS 7可以抑制5α-二氢睾酮，但其对前列腺癌细胞的作用似乎与雄激素代谢无关。当比较三种广泛研究的前列腺癌细胞系时，我们观察到DHRS 7和EGFR表达之间的负相关性。DHRS 7敲低增强EGFR表达，而EGFR敲低倾向于增加DHRS 7表达。重要的是，DHRS 7表达与EGFR表达呈负相关，与前列腺癌患者的生存率呈正相关。这项研究表明，DHRS 7通过调节前列腺癌中EGFR的表达而发挥肿瘤抑制作用。前列腺癌（PCa）是男性最常见的恶性肿瘤之一，通常对初始治疗有反应，但对治疗的抵抗通常导致转移和死亡。脱氢酶/还原酶7（DHRS 7，SDR 34 C1）是一种没有已知生理功能的“孤儿”酶。先前发现DHRS 7在更高阶段的PCa中减少，并且siRNA介导的敲低增加了LNCaP细胞的侵袭性。为了进一步探索DHRS 7在PCa中的作用，我们分析了DHRS 7敲低后LNCaP细胞的蛋白质组，以评估潜在的改变途径。虽然DHRS 7能够抑制5α-二氢睾酮，但DHRS 7敲低并不影响雄激素受体（AR）靶基因的表达，并且其对PCa细胞的作用似乎是雄激素非依赖性的。重要的是，蛋白质组分析显示表皮生长因子受体（EGFR）的表达增加，这是通过RT-qPCR和蛋白质印迹法证实的。AR阳性LNCaP与AR阴性PC-3和DU 145 PCa细胞系的比较揭示了DHRS 7和EGFR表达之间的负相关性。相反，EGFR敲低增强了这些细胞中DHRS 7的表达。重要的是，对患者样本的分析揭示了DHRS 7和EGFR表达之间在mRNA和蛋白质水平上的负相关性，并且DHRS 7表达与患者存活率呈正相关。这些结果表明DHRS 7在PCa中具有保护作用。
Prostate cancer is one of the most common malignancies in men. Current therapies are initially effective but resistance often develops, leading to tumor recurrence and death. Further research on new players, mechanisms involved in prostate cancer, and therapy resistance is needed. We studied the role of DHRS7, a potential tumor suppressor with currently unknown physiological function, in prostate cancer cells using proteome and gene expression analyses. Despite the fact that DHRS7 can inactivate 5α-dihydrotestosterone, its effect on prostate cancer cells seems to be unrelated to androgen metabolism. When comparing three widely studied prostate cancer cell lines, we observed a negative correlation between DHRS7 and EGFR expression. DHRS7 knockdown enhanced EGFR expression, while knockdown of EGFR tended to increase DHRS7 expression. Importantly, DHRS7 expression negatively correlates with EGFR expression and positively with survival rates in prostate cancer patients. This study suggests a tumor-suppressor role for DHRS7 by modulating EGFR expression in prostate cancer. Prostate cancer (PCa), one of the most common malignancies in men, typically responds to initial treatment, but resistance to therapy often leads to metastases and death. The dehydrogenase/reductase 7 (DHRS7, SDR34C1) is an “orphan” enzyme without known physiological function. DHRS7 was previously found to be decreased in higher-stage PCa, and siRNA-mediated knockdown increased the aggressiveness of LNCaP cells. To further explore the role of DHRS7 in PCa, we analyzed the proteome of LNCaP cells following DHRS7 knockdown to assess potentially altered pathways. Although DHRS7 is able to inactivate 5α-dihydrotestosterone, DHRS7 knockdown did not affect androgen receptor (AR) target gene expression, and its effect on PCa cells seems to be androgen-independent. Importantly, proteome analyses revealed increased expression of epidermal growth factor receptor (EGFR), which was confirmed by RT-qPCR and Western blotting. Comparison of AR-positive LNCaP with AR-negative PC-3 and DU145 PCa cell lines revealed a negative correlation between DHRS7 and EGFR expression. Conversely, EGFR knockdown enhanced DHRS7 expression in these cells. Importantly, analysis of patient samples revealed a negative correlation between DHRS7 and EGFR expression, both at the mRNA and protein levels, and DHRS7 expression correlated positively with patient survival rates. These results suggest a protective role for DHRS7 in PCa.
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影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
--
作者：
Bauman, DR;Steckelbroeck, S;Penning, TM
通讯作者：
Penning, TM
DOI：
10.1152/ajpendo.00708.2006
发表时间：
2007-06-01
影响因子：
5.1
作者：
Grossmann, Claudia;Krug, Alexander W.;Gekle, Michael
通讯作者：
Gekle, Michael
影响因子：
6
作者：
Campbell, CL;Jiang, Z;Savarese, TM
通讯作者：
Savarese, TM