Abstract |
Heat-shock protein 90 (Hsp90) inhibitor downregulates c-Myc expression and upregulates the expression of tumor repressor proteins such as p53 and pRB, inhibiting the G1/S transition and causing G2/M arrest during cell cycle progression. The cycle progression is extensively controlled by the pRB/E2F signaling pathway. E2F is released from the pRB/E2F complex with the phosphorylation of pRB by cyclin- cyclin-dependent kinase (CDK) complexes. The released E2F promotes the transcription of target genes involved in cell cycle progression. The pRB/E2F signaling pathway is controlled by DNA methyltransferase-1 (Dnmt-1). The elevated expression of Dnmt-1 has been reported in carcinomas of the colon, lung and prostate. A defect of pRB expression in Rb -/- cancer cells is caused by the aberrant methylation of CpG in the Rb promoter. The Hsp90 inhibitor disrupts the Dnmt-1/Hsp90 association and upregulates pRB expression. In this review, the Hsp90 inhibitors that show promise for cancer therapy are summarized.
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Authors | Hiroshi Yamaki, Motowo Nakajima, Kumiko W Shimotohno, Nobuo Tanaka |
Journal | The Journal of antibiotics
(J Antibiot (Tokyo))
Vol. 64
Issue 9
Pg. 635-44
(Sep 2011)
ISSN: 1881-1469 [Electronic] England |
PMID | 21811259
(Publication Type: Journal Article, Review)
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Chemical References |
- Antineoplastic Agents
- HSP90 Heat-Shock Proteins
- Retinoblastoma Protein
- Tumor Suppressor Protein p53
- Tumor Suppressor Proteins
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Cell Cycle
(genetics)
- Gene Expression Regulation, Neoplastic
- HSP90 Heat-Shock Proteins
(antagonists & inhibitors)
- Humans
- Neoplasms
(drug therapy, genetics, pathology)
- Retinoblastoma Protein
(genetics)
- Signal Transduction
(genetics)
- Tumor Suppressor Protein p53
(genetics)
- Tumor Suppressor Proteins
(genetics)
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