Reduction in Nuclear Size by DHRS7 in Prostate Cancer Cells and by Estradiol Propionate in DHRS7-Depleted Cells.

Reduction in Nuclear Size by DHRS7 in Prostate Cancer Cells and by Estradiol Propionate in DHRS7-Depleted Cells.
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在前列腺癌细胞中通过DHRS7和在DHRS7耗尽的细胞中通过丙酸雌二醇减少核大小。

DOI:
10.3390/cells13010057
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发表时间:
2023-12-27
期刊:
影响因子:
6
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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增大的核大小与前列腺癌较低的生存率和较高的分级相关。短链脱氢酶/还原酶(SDR)家族成员DHRS7被认为是用于前列腺癌分级的生物标志物,因为它在高级别肿瘤中大部分丢失。在这里,我们发现LNCaP前列腺癌细胞系中DHRS7的减少会增加细胞核大小,这可能解释了在高级别前列腺肿瘤中观察到的核大小增加。在正常低DHRS7水平的PC3前列腺癌细胞系中,外源性DHRS7的表达相应地减少了细胞核的大小。我们分别测试了Microsource Spectrum文库中的80种化合物恢复PC3细胞正常较小核尺寸的能力,发现丙酸雌二醇在PC3细胞中具有与DHRS7重新表达相同的效果。然而,该药对LNCaP细胞或重新表达DHRS7的PC3细胞没有影响。我们推测,单独报道的雌激素对雄激素非依赖性前列腺癌的有益作用可能只发生在DHRS7缺失/核大小增加的情况下,因此提出DHRS7水平和核大小作为雌激素治疗可能有效性的潜在生物标志物。
Increased nuclear size correlates with lower survival rates and higher grades for prostate cancer. The short-chain dehydrogenase/reductase (SDR) family member DHRS7 was suggested as a biomarker for use in prostate cancer grading because it is largely lost in higher-grade tumors. Here, we found that reduction in DHRS7 from the LNCaP prostate cancer cell line with normally high levels of DHRS7 increases nuclear size, potentially explaining the nuclear size increase observed in higher-grade prostate tumors where it is lost. An exogenous expression of DHRS7 in the PC3 prostate cancer cell line with normally low DHRS7 levels correspondingly decreases nuclear size. We separately tested 80 compounds from the Microsource Spectrum library for their ability to restore normal smaller nuclear size to PC3 cells, finding that estradiol propionate had the same effect as the re-expression of DHRS7 in PC3 cells. However, the drug had no effect on LNCaP cells or PC3 cells re-expressing DHRS7. We speculate that separately reported beneficial effects of estrogens in androgen-independent prostate cancer may only occur with the loss of DHRS7/ increased nuclear size, and thus propose DHRS7 levels and nuclear size as potential biomarkers for the likely effectiveness of estrogen-based treatments.
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。
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