CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1

视网膜母细胞瘤 癌症研究 视网膜母细胞瘤蛋白 细胞周期 医学 膀胱癌 癌症 顺铂 细胞周期蛋白D1 E2F型 细胞凋亡 E2F1 细胞生长 生物 内科学 基因 化疗 遗传学
作者
Anuja Sathe,Nicole Rachel Koshy,Sebastian C. Schmid,Mark Thalgott,Sarah M. Schwarzenböck,Bernd J. Krause,Per Sonne Holm,Juergen E. Gschwend,Margitta Retz,Roman Nawroth
出处
期刊:The Journal of Urology [Lippincott Williams & Wilkins]
卷期号:195 (3): 771-779 被引量:46
标识
DOI:10.1016/j.juro.2015.08.082
摘要

The retinoblastoma signaling network is frequently altered in advanced bladder cancer. We investigated the potential of CDK4/6 as a therapeutic target and determined biomarkers for patient stratification.Genetic alterations were analyzed using public databases, including TCGA (The Cancer Genome Atlas), COSMIC (Catalogue of Somatic Mutations in Cancer) and CCLE (Cancer Cell Line Encyclopedia). Effects of the CDK4/6-inhibitor PD-0332991 or LY2835219 were examined in 10 bladder cancer cell lines by immunoblot, cell viability, apoptosis and cell cycle progression. Efficacy of the PD-0332991 and cisplatin combination was analyzed using the combination index. Gene expression level was determined by quantitative polymerase chain reaction. Cytomegalovirus promoter regulated recombinant retinoblastoma was used for reconstitution. Three-dimensional xenografts were grown on chicken chorioallantoic membrane and analyzed by measuring tumor weight and immunohistochemical expression of total retinoblastoma and Ki-67.PD-0332991 treatment decreased the proliferation of retinoblastoma positive bladder cancer cell lines and was synergistic in combination with cisplatin. PD-0332991 or LY2835219 treatment decreased the phosphorylation, total protein and transcript level of retinoblastoma. Treatment resulted in a decrease in E2F target gene expression (CCNA2 and CCNE2) and cell cycle progression from G0/G1 to the S-phase but did not affect apoptosis. In retinoblastoma negative cells reconstituted with recombinant retinoblastoma PD-0332991 affected only phosphorylation and not the total retinoblastoma level. These cells remained resistant to treatment. In 3-dimensional retinoblastoma xenografts, treatment resulted in reduced tumor weight and decreased expression of total retinoblastoma and Ki-67.We provide preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
文献互助1完成签到 ,获得积分10
2秒前
lyc45491314发布了新的文献求助10
2秒前
汉堡包应助牛虻采纳,获得10
2秒前
4秒前
4秒前
Picky发布了新的文献求助10
5秒前
刘雪松完成签到,获得积分10
6秒前
情怀应助K甲采纳,获得10
7秒前
8秒前
9秒前
10秒前
11秒前
阿珍发布了新的文献求助10
12秒前
wusj120发布了新的文献求助10
13秒前
14秒前
rrrrrwwwww发布了新的文献求助10
15秒前
16秒前
hua发布了新的文献求助10
16秒前
思源应助17采纳,获得10
16秒前
量子星尘发布了新的文献求助10
17秒前
17秒前
石头完成签到,获得积分10
17秒前
顺心夏山关注了科研通微信公众号
18秒前
K甲完成签到,获得积分20
18秒前
18秒前
lyc45491314发布了新的文献求助10
18秒前
19秒前
20秒前
20秒前
小二郎应助Ayao采纳,获得10
21秒前
Lina发布了新的文献求助10
22秒前
23秒前
桑叶发布了新的文献求助10
24秒前
K甲发布了新的文献求助10
25秒前
Akim应助澡雪采纳,获得10
27秒前
HeJiangle发布了新的文献求助10
27秒前
29秒前
脑洞疼应助yyyhhh采纳,获得10
29秒前
wusj120完成签到,获得积分10
30秒前
30秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975836
求助须知:如何正确求助?哪些是违规求助? 3520174
关于积分的说明 11201364
捐赠科研通 3256576
什么是DOI,文献DOI怎么找? 1798362
邀请新用户注册赠送积分活动 877539
科研通“疑难数据库(出版商)”最低求助积分说明 806426