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| 1 | Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β-catenin signaling显示文摘Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D,1,25-dihydroxy-vitamin D [1,25(OH)2 D] are mediated through binding to the vitamin D receptor(VDR). Here,we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad(MDA-MB-231),subcutaneously(PC3) or intra-tibially(both cell lines) in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls.These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/β-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1,interleukin-6(IL-6), and IL-8. Stabilization of β-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer. | Yu Zheng Trupti Trivedi Ruby CY Lin Colette Fong-Yee Rick Nolte Jeline Manibo Yunzhao Chen Musharraf Hossain Konstantin Horas Colin Dunstan Hong Zhou Markus J Seibel | 2017 | Bone Research2017，5，3： | 4 |
| 2 | The effect of durationof macular detachment on results after the scleral buckle repair of primary macular-off retinal detachments 显示文摘 | Hassan TS Sarrafizadeh R Ruby A J | 2002 | Ophthalmology2002，109，1： | 1 |
| 3 | Requirement for glycogen synthase kinase-3beta in cell survival and NF- kappaB activation 显示文摘 | Hoeflich KP Luo J Rubie EA | 2000 | Nature2000，406，6791： | 1 |
| 4 | Catheter related infec- tions and associated septicemia 显示文摘 | Norwood S Ruby A Civetta J | 1991 | Chest1991，99，4： | 1 |
| 5 | The mechanics of benign paroxysmal vertigo显示文摘 | Hall S F Ruby R R Mcclure J A | 1979 | Otolaryngol1979，8，2： | 1 |
| 6 | PCS 1 900 MHz duplexer using thin film bulk acoustic resonators (FBARs) 显示文摘 | RUBY R BRADLEY P LARSON J DIII | 1999 | Electronic Letters1999，35，10： | 1 |
| 7 | Membrane proteomic analysis of Arabidopsis thaliana using alternative solubilization techniques 显示文摘 | Mitra S K Gantt J A Ruby J F | 2007 | Journal of Proteome Research2007，6，5： | 1 |
| 8 | Pars plana vitrectomy with removal of the internal limiting membrane in the treatment of persistent diabetic macular edema显示文摘 | Recchia F M Ruby A J Carvalho Recchia C A | 2005 | Am J Ophthalmol2005，139，： | 1 |
| 9 | Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation显示文摘 | Hoeflich KP Luo J Rubie EA | 2000 | Nature2000，406，6791： | 1 |
| 10 | PCS 1 900 MHz duplexer using thin film bulk acoustic resonator (FBARs)显示文摘 | RUBY R BRADLEY P LARSON J | 1999 | Electron Lett1999，35，7： | 1 |
| 11 | Noise suppression by noise 显示文摘 | J M G Vilar J M Rubi | 2001 | Physical Review Letters2001，86，6： | 1 |
| 12 | Four yeast spliceosomal proteins(PRP5,PRP9,PRP11,and PRP21)interact to promote U2 snRNP bindingto pre-Mrna显示文摘 | RUBY S W CHANG T H ABELSON J | 1993 | Genes&Development1993，7，10： | 1 |
| 13 | Stochastic Resonance in Noisy Nondynamical Systems显示文摘 | Vilar J Gomila G Rubi J | 1998 | Physical Review Letters1998，81，1： | 1 |
| 14 | Intronic microRNA precursors that bypass Drosha processing显示文摘 | Ruby J G Jan C H Bartel D P | 2007 | Nature2007，448，7149： | 1 |
| 15 | ZnO nanostructures as efficient antireflection layers in solar cells 显示文摘 | LEE Y J RUBY D S PETERS D W | 2008 | Nano Letters2008，8，5： | 1 |
| 16 | How self-generated thought shapes mood-the relation between mind-wandering and mood depends on the socio-temporal content of thoughts 显示文摘 | RUBY F J SMALLWOOD J ENGEN H | 2013 | PLoS ONE2013，8，77： | 1 |
| 17 | Resveratrol delays replicative senescence of human mesothelial cells via mobilization of antioxidative and DNA repair mechanisms显示文摘 | Mikula-Pietrasik J Kuczmarska A Rubis B | 2012 | Free Radic Biol Med2012，52，1112： | 1 |
| 18 | Requeirment for glycogen synthase kinase-3 β in cell survival and NF- κ B activation 显示文摘 | Hoeflich K P Luo J Rubie E A | 2000 | Nature2000，406，： | 1 |
| 19 | Biochemical markers and cardiac troponin Ⅰ release after radiofrequency catheter ablation显示文摘 | Madrid AH Del Rey JM Rubi J | 1998 | Approach to size of necrosis1998，136，： | 1 |
| 20 | Incidence of retinal detachment and visual outcome in eyes presenting with posterior vitreous separation and dense fundus-obscuring vitreous haemorrhage显示文摘 | SARRAFIZADEH R HASSAN T S RUBY A J | 2001 | Ophthalmology2001，108，： | 1 |
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