Monitoring the induction of heat shock factor 1/heat shock protein 70 expression following 17-allylamino-demethoxygeldanamycin treatment by positron emission tomography and optical reporter gene imaging Journal Article
| Authors: | Doubrovin, M.; Che, J. T.; Serganova, I.; Moroz, E.; Solit, D. B.; Ageyeva, L.; Kochetkov, T.; Pillarsetty, N.; Finn, R.; Rosen, N.; Blasberg, R. G. |
| Article Title: | Monitoring the induction of heat shock factor 1/heat shock protein 70 expression following 17-allylamino-demethoxygeldanamycin treatment by positron emission tomography and optical reporter gene imaging |
| Abstract: | The cell response to proteotoxic cell stresses is mediated primarily through activation of heat shock factor 1 (HSF1). This transcription factor plays a major role in the regulation of the heat shock proteins (HSPs), including HSP70. We demonstrate that an [ 124I]iodide-pQHNIG70 positron emission tomography (PET) reporter system that includes an inducible HSP70 promoter can be used to image and monitor the activation of the HSF1/HSP70 transcription factor in response to drug treatment (17- allylaminodemethoxygeldanamycin [17-AAG]). We developed a dual imaging reporter (pQHNIG70) for noninvasive imaging of the heat shock response in cell culture and living animals previously and now study HSF1/HSP70 reporter activation in both cell culture and tumorbearing animals following exposure to 17-AAG. 17-AAG (10-1,000 nM) induced reporter expression; a 23-fold increase was observed by 60 hours. Good correspondence between reporter expression and HSP70 protein levels were observed. MicroPET imaging based on [ 124I]iodide accumulation in pQHNIG70-transduced RG2 xenografts showed a significant 6.2-fold reporter response to 17-AAG, with a corresponding increase in tumor HSP70 and in tumor human sodium iodide symporter and green fluorescent protein reporter proteins. The HSF1 reporter system can be used to screen anticancer drugs for induction of cytotoxic stress and HSF1 activation both in vitro and in vivo. © 2012 Decker Publishing. |
| Keywords: | genetics; positron emission tomography; methodology; metabolism; animals; genes; green fluorescent protein; cell line; transcription factor; diagnostic imaging; transcription factors; blotting, western; tumors; western blotting; positron-emission tomography; reporter gene; tanespimycin; genes, reporter; heat shock protein 70; cytotoxic; animal cell culture; heat shock response; drug therapy; in-vitro; reporter systems; benzoquinones; lactams, macrocyclic; hsp70 heat-shock proteins; cell stress; anticancer drug; 17-(allylamino)-17-demethoxygeldanamycin; benzoquinone derivative; macrocyclic lactam; micropet; protein level; heat shock protein; non-invasive imaging; living animals; cell response; dual imaging; heat shock factors; heat-shock factor 1; reporter protein; shock proteins; sodium iodides |
| Journal Title: | Molecular Imaging |
| Volume: | 11 |
| Issue: | 1 |
| ISSN: | 1535-3508 |
| Publisher: | Sage Publications, Inc. |
| Date Published: | 2012-01-01 |
| Start Page: | 67 |
| End Page: | 76 |
| Language: | English |
| DOI: | 10.2310/7290.2011.00028 |
| PROVIDER: | scopus |
| PUBMED: | 22418029 |
| PMCID: | PMC5400108 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 April 2012" - "Source: Scopus" |
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