Induction of the human heat shock promoter HSP70B by nutritional stress: implications for cancer gene therapy.
Cancer Invest
; 26(6): 553-61, 2008 Jul.
Article
en En
| MEDLINE
| ID: mdl-18584345
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 ANDMETHODS:
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.
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Terapias_biologicas
/
Trofoterapia
Asunto principal:
Estrés Fisiológico
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Terapia Genética
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Activación Transcripcional
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Regiones Promotoras Genéticas
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Interleucina-12
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Proteínas HSP70 de Choque Térmico
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Cancer Invest
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos