Abstract | BACKGROUND: METHODS: Quantitative measurements of immunohistochemical expression of TP53INP1 using high-throughput densitometry, assessed on digitized microscopic tissue micro-array images were correlated with hormone therapy (HT) status in human PC. Northern blot analysis of TP53INP1 after castration was performed in LNCaP xenograft. Treatment of CR C4-2 tumor cells in vitro with TP53INP1 ASO was analyzed. We also analyzed the effect of TP53INP1 ASO treatment in vivo on tumor xenograft growth. RESULTS: TP53INP1 protein expression decreases during HT and increases after HT in human CRPC. TP53INP1 mRNA increases significantly in CR tumors of LNCaP xenograft. Moreover, treatment of CR C4-2 cells with TP53INP1 ASO downregulates TP53INP1 protein level, inhibits proliferation, and induces apoptosis. Finally, in vivo, TP53INP1 ASO treatment significantly inhibits the tumoral progression of CR C4-2 xenograft and enhances docetaxel cytotoxicity. CONCLUSIONS: These results suggest that TP53INP1 could be considered as a relevant-specific target for molecular therapy of CRPC.
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Authors | Sophie Giusiano, Virginie Baylot, Claudia Andrieu, Ladan Fazli, Martin Gleave, Juan Lucio Iovanna, Colette Taranger-Charpin, Stéphane Garcia, Palma Rocchi |
Journal | The Prostate
(Prostate)
Vol. 72
Issue 12
Pg. 1286-94
(Sep 01 2012)
ISSN: 1097-0045 [Electronic] United States |
PMID | 22213058
(Publication Type: Journal Article)
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Copyright | Copyright © 2011 Wiley Periodicals, Inc. |
Chemical References |
- Apoptosis Regulatory Proteins
- Carrier Proteins
- Heat-Shock Proteins
- Oligonucleotides, Antisense
- TP53INP1 protein, human
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Topics |
- Animals
- Apoptosis Regulatory Proteins
(antagonists & inhibitors)
- Carrier Proteins
(antagonists & inhibitors, biosynthesis)
- Cell Line, Tumor
- Drug Delivery Systems
(methods)
- Heat-Shock Proteins
(antagonists & inhibitors, biosynthesis)
- Humans
- Male
- Mice
- Mice, Nude
- Oligonucleotides, Antisense
(administration & dosage)
- Orchiectomy
- Prostatic Neoplasms
(drug therapy, metabolism, pathology)
- Xenograft Model Antitumor Assays
(methods)
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