Induction of the human heat shock promoter HSP70B by nutritional stress

Implications for cancer gene therapy

Farzan Siddiqui, Paul R. Avery, Chuan Yuan Li, Xiuwu Zhang, Susan M. LaRue, Mark W. Dewhirst, Robert L. Ullrich

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: We designed and tested, in vitro, an adenoviral construct containing the feline interleukin-12 (IL-12) gene under control of the heat-inducible promoter HSP70B. This construct, AdhspfIL12, was used in a phase I trial in feline soft tissue sarcomas. During the course of our experiments, we noted that IL-12 was being produced in the transfected Crandell Feline Kidney (CrFK) cells under certain conditions even in the absence of hyperthermia. This observation was further explored to identify the cause of this unintended HSP70B induction. Materials and Methods: We used real-time PCR as a sensitive method to quantitatively detect the presence of even small amounts of IL-12 mRNA. This served as a surrogate indicator of HSP70B induction. Various conditions were tested to induce the heat shock promoter, including nutritional deprivation, radiation and changes in pH. Results: Nutritional stresses, specifically the absence of glucose and glutamine, could induce the heat shock promoter, thus, resulting in production of the downstream gene product. Other factors known to trigger the heat shock response, pH change, and reactive oxygen species production were also studied but were not found to contribute to heat shock promoter induction in our setting. Conclusions: The human heat shock promoter (HSP70B) is reported to be an efficient and tightly regulated promoter. We discovered, using sensitive real-time PCR techniques, that it can also be induced in response to cellular nutrient stresses. The pros and cons of this phenomenon and its implications for cancer gene therapy are discussed.

Original languageEnglish (US)
Pages (from-to)553-561
Number of pages9
JournalCancer Investigation
Volume26
Issue number6
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Neoplasm Genes
Genetic Therapy
Shock
Hot Temperature
Felidae
Interleukin-12
Real-Time Polymerase Chain Reaction
Heat-Shock Response
Glutamine
Sarcoma
Genes
Reactive Oxygen Species
Fever
Radiation
Kidney
Glucose
Food
Messenger RNA

Keywords

  • Gene therapy
  • Glucose
  • Glutamine
  • Heat shock promoter

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Siddiqui, F., Avery, P. R., Li, C. Y., Zhang, X., LaRue, S. M., Dewhirst, M. W., & Ullrich, R. L. (2008). Induction of the human heat shock promoter HSP70B by nutritional stress: Implications for cancer gene therapy. Cancer Investigation, 26(6), 553-561. https://doi.org/10.1080/07357900701788015

Induction of the human heat shock promoter HSP70B by nutritional stress : Implications for cancer gene therapy. / Siddiqui, Farzan; Avery, Paul R.; Li, Chuan Yuan; Zhang, Xiuwu; LaRue, Susan M.; Dewhirst, Mark W.; Ullrich, Robert L.

In: Cancer Investigation, Vol. 26, No. 6, 07.2008, p. 553-561.

Research output: Contribution to journalArticle

Siddiqui, F, Avery, PR, Li, CY, Zhang, X, LaRue, SM, Dewhirst, MW & Ullrich, RL 2008, 'Induction of the human heat shock promoter HSP70B by nutritional stress: Implications for cancer gene therapy', Cancer Investigation, vol. 26, no. 6, pp. 553-561. https://doi.org/10.1080/07357900701788015
Siddiqui, Farzan ; Avery, Paul R. ; Li, Chuan Yuan ; Zhang, Xiuwu ; LaRue, Susan M. ; Dewhirst, Mark W. ; Ullrich, Robert L. / Induction of the human heat shock promoter HSP70B by nutritional stress : Implications for cancer gene therapy. In: Cancer Investigation. 2008 ; Vol. 26, No. 6. pp. 553-561.
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