Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer Journal Article

  


Authors: Rodina, A.; Vilenchik, M.; Moulick, K.; Aguirre, J.; Kim, J.; Chiang, A.; Litz, J.; Clement, C. C.; Kang, Y.; She, Y.; Wu, N.; Felts, S.; Wipf, P.; Massague, J.; Jiang, X.; Brodsky, J. L.; Krystal, G. W.; Chiosis, G.
Article Title: Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer
Abstract: The heat shock protein 90 (Hsp90) has a critical role in malignant transformation. Whereas its ability to maintain the functional conformations of mutant and aberrant oncoproteins is established, a transformation-specific regulation of the antiapoptotic phenotype by Hsp90 is poorly understood. By using selective compounds, we have discovered that small-cell lung carcinoma is a distinctive cellular system in which apoptosis is mainly regulated by Hsp90. Unlike the well-characterized antiapoptotic chaperone Hsp70, Hsp90 is not a general inhibitor of apoptosis, but it assumes this role in systems such as small-cell lung carcinoma, in which apoptosis is uniquely dependent on and effected through the intrinsic pathway, without involvement of caspase elements upstream of mitochondria or alternate pathways that are not apoptosome- channeled. These results provide important evidence for a transformation- specific interplay between chaperones in regulating apoptosis in malignant cells. © 2007 Nature Publishing Group.
Keywords: unclassified drug; doxorubicin; nonhuman; antineoplastic agents; gemcitabine; topotecan; apoptosis; etoposide; lung neoplasms; dose-response relationship, drug; drug screening assays, antitumor; caspase inhibitor; cell line, tumor; drug design; time factors; carcinogenesis; cell transformation, neoplastic; lung small cell cancer; gene expression regulation, neoplastic; quercetin; breast carcinoma; mitoxantrone; 1-phosphatidylinositol 3-kinase; daunorubicin; 8 (6 iodobenzo[d][1,3]dioxol 5 ylthio) 9 [3 (isopropylamino)propyl] 9h purin 6 amine; heat shock protein 90 inhibitor; heat shock protein 90; hsp90 heat-shock proteins; epirubicin; heat shock protein 70; cell strain mcf 7; mitochondrion; models, chemical; carcinoma, small cell; geldanamycin; radicicol; cycloproparadicicol; lactone derivative; puh 58; puh 71; 17 allylamino 17 demethoxygeldanamycin; 17 dimethylaminoethylamino 17 demethoxygeldanamycin; 8 (2 chloro 3,4,5 trimethoxybenzyl) 2 fluoro 9 (pent 4 ynyl) 9h purin 6 amine; 8 (6 bromobenzo[d][13]dioxol 5 ylthio) 9 (pent 4 ynyl) 9h purin 6 amine; benzyloxycarbonylleucylglutamylhistidylaspartyl fluoromethyl ketone; caspase 9 inhibitor; heat shock protein 70 inhibitor; knk 437; macrolactone derivative; mal 3 101; menogaril; pu 24fci
Journal Title: Nature Chemical Biology
Volume: 3
Issue: 8
ISSN: 1552-4450
Publisher: Nature Publishing Group  
Date Published: 2007-08-01
Start Page: 498
End Page: 507
Language: English
DOI: 10.1038/nchembio.2007.10
PUBMED: 17603540
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-34447498813&partnerID=40&md5=dca2f4fc1d951a018f991d1bb2102b5b
Notes: --- - "Cited By (since 1996): 55" - "Export Date: 17 November 2011" - "Source: Scopus"
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MSK Authors
  1. Maria Vilenchik
    7 Vilenchik
  2. Cristina C Clement
    12 Clement
  3. Anne Chi-An Chiang
    13 Chiang
  4. Yuhong She
    31 She
  5. Joan Massague
    389 Massague
  6. Nian Wu
    32 Wu
  7. Kamalika Moulick
    16 Moulick
  8. Anna Rodina Balingcongan
    55 Rodina Balingcongan
  9. Gabriela Chiosis
    279 Chiosis
  10. Xuejun Jiang
    121 Jiang
  11. Yanlong Kang
    22 Kang
  12. Julia Aguirre
    15 Aguirre
  13. Joungnam Kim
    14 Kim
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