RPS2: a novel therapeutic target in prostate cancer.
RPS2: a novel therapeutic target in prostate cancer.
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DOI：
10.1186/1756-9966-28-6
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发表时间：
2009-01-12
期刊：
影响因子：
--
通讯作者：
Stearns ME
中科院分区：
文献类型：
--
作者：
Wang M;Hu Y;Stearns ME
许多研究表明，不同的核糖体蛋白（即S3 a，L10，L16）的过表达可能在癌症中起重要作用。我们以前曾报道过，RPS 2，一个33 Kda的核糖体蛋白在恶性前列腺癌细胞系和存档的肿瘤标本中过表达。因此，RPS 2或其他异常过表达的核糖体蛋白可能促进癌症并且是用于治疗该疾病的极好的治疗靶标。Western印迹和RT-PCR已被用于测量和比较RPS 2在各种恶性前列腺癌细胞系以及正常和良性细胞系中的表达水平。我们已经开发了一种'核酶样' DNAZYM-1 P '10-23'基序寡核苷酸，并通过RT-PCR和Western印迹检测它是否靶向不同细胞系中的RPS 2。进行生长和凋亡测定以测量RPS 2的DNAZYM-1 P“敲低”是否影响细胞增殖或存活。我们还用PC-3 ML细胞开发了一种SCID小鼠肿瘤模型，以确定靶向RPS 2的DNAZYM-1 P是否会影响体内肿瘤生长和小鼠存活率。Western印迹显示PC-3 ML、LNCaP、CPTX-1532和pBABE-cmyc稳定转染的IBC-10a细胞都过表达RPS 2，而IBC-10a亲本、NPTX-1532和BPH-1细胞或小鼠NIH-3 T3细胞表达几乎检测不到水平的RPS 2。RT-PCR分析显示，靶向RPS 2的DNAZYM-1 P在体外“敲低"恶性细胞（即PC-3 ML细胞）中的RPS 2表达。DNAZYM-1 P对前列腺癌细胞株IBC-10a和NPTX-1532的增殖有抑制作用，并能诱导细胞凋亡，但对正常细胞株IBC-10a和NPTX-1532的增殖无明显影响。最后，SCID小鼠肿瘤建模研究表明，DNAZYM-1 P通过PC-3 ML细胞阻断肿瘤生长和转移，并最终在局部或全身静脉内递送后根除肿瘤。小鼠存活研究显示，在用DNAZYM-1 P全身治疗的小鼠中，无病存活率存在剂量依赖性增加（即小鼠存活从0%增加至100%）。总之，我们首次证明了RPS 2的治疗靶向是临床前肿瘤建模研究中根除前列腺癌的一种极好方法。
A number of studies have previously shown that the over expression of different ribosomal proteins might play an important role in cancer (i.e. S3a, L10, L16). We have previously reported that RPS2, a 33 Kda ribosomal protein was over expressed in malignant prostate cancer cell lines and in archived tumor specimens. Thus, RPS2 or other aberrantly over-expressed ribosomal proteins might promote cancer and be excellent therapeutic targets for treatment of the disease. Western blotting and RT-PCR have been used to measure and compare the levels of expression of RPS2 in a variety of malignant prostate cancer cell lines, plus normal and benign cells lines. We have developed a 'ribozyme-like' DNAZYM-1P '10–23' motif oligonucleotide and examined whether it targets RPS2 in different cell lines by RT-PCR and Western blots. Growth and apoptosis assays were carried out to measure whether DNAZYM-1P 'knock-down' of RPS2 influenced cell proliferation or survival. We have also developed a SCID mouse tumor model with PC-3ML cells to determine whether DNAZYM-1P targeting of RPS2 compromised tumor growth and mouse survival rates in vivo. Western blots showed that PC-3ML, LNCaP, CPTX-1532, and pBABE-cmyc stably transfected IBC-10a cells all over-expressed RPS2, whereas IBC-10a parent, NPTX-1532, and BPH-1 cells or mouse NIH-3T3 cells expressed barely detectable levels of RPS2. RT-PCR assays showed that DNAZYM-1P, which targeted RPS2, 'knocked-down' RPS2 expression in the malignant cells (i.e. PC-3ML cells) in vitro. The DNAZYM-1P also inhibited cell growth and induced apoptosis in the malignant prostate cells, but had little effect on the normal IBC-10a or NPTX-1532 cell lines. Finally, SCID mouse tumor modeling studies showed that DNAZYM-1P blocked tumor growth and metastasis by PC-3ML cells and eventually eradicated tumors following localized or systemic i.v. delivery. Mouse survival studies revealed that there was a dosage dependent increase in disease free survival rates in mice treated systemically with DNAZYM-1P (i.e. mouse survival increased from 0% to 100%). In sum, we have shown for the first time that therapeutic targeting of RPS2 is an excellent approach for the eradication of prostate cancer in preclinical tumor modeling studies.
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影响因子：
4.6
作者：
CHIAO, PJ;SHIN, DM;TAINSKY, MA
通讯作者：
TAINSKY, MA
影响因子：
4.8
作者：
Sun, LQ;Cairns, MJ;King, A
通讯作者：
King, A
影响因子：
5.3
作者：
HOLT, JT;REDNER, RL;NIENHUIS, AW
通讯作者：
NIENHUIS, AW
DOI：
10.1006/bbrc.1996.1277
发表时间：
1996-08-23
影响因子：
3.1
作者：
Chan, YL;Diaz, JJ;Wool, IG
通讯作者：
Wool, IG
影响因子：
2.9
作者：
WANG, M;STEARNS, ME
通讯作者：
STEARNS, ME