Any extracts used in the following article are for non commercial research and educational purposes only and may be subject to copyright from their respective owners.
Cancer-inducible Transgene Expression by the Grp94 Promoter
Spontaneous Activation in Tumors of Various Origins and Cancer-associated Macrophages
Ramachandra K. Reddy, Louis Dubeau, Heather Kleiner, Tyler Parr, Peter Nichols, Bryce Ko, Dezheng Dong, Howard Ko, Changhui Mao, John DiGiovanni and Amy S. Lee
DOI: Published December 2002
Abstract
A major challenge in treating cancer is the difficulty of bringing therapy to poorly perfused areas of solid tumors, which are often most resistant to chemotherapy and radiation. GRP94 is a chaperone protein localized in the endoplasmic reticulum with antiapoptotic properties. We report here that in vitro the proximal murine grp94 promoter is regulated differently from the hypoxia response element fused to the SV40 minimal promoter, with glucose starvation as an inducer of grp94 but a potent repressor of the hypoxia response element/SV40 fusion promoter. Through the use of transgenic mouse models, we showed that LacZ transgene expression driven by the grp94 promoter was strongly activated not only in spontaneous but also in a variety of chemically induced tumors. We additionally discovered that macrophages in the vicinity of malignant tumor showed a high level of transgene expression, consistent with intense β-galactosidase staining at boundaries between viable tumor cells and necrotic areas. Isolated macrophages also showed grp94 mRNA and transgene activation under glucose starvation in vitro. In contrast, transgene activity was not detected in the normal tissue counterparts of any of the malignant tumors examined or macrophages associated with normal organs. These studies provide direct evidence that the tumor microenvironment is a potent physiological inducer of the grp94 promoter. The unique properties of the grp94 promoter suggest that it may offer a novel tool for directing transcription of therapeutic agents to tumors particularly in resistant regions bordering necrotic areas, delivered through standard vectors or macrophages.
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Spike protein (inc vax) induced immunodeficiency & carcinogenesis megathread #17: Cancer-inducible Transgene Expression by the Grp94 Promoter
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Any extracts used in the following article are for non commercial research and educational purposes only and may be subject to copyright from their respective owners.
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Great work by @n3636 and @parsifaler.
Roles of spike protein in the pathogenesis of SARS coronavirus
DY Jin, BJ Zheng
Department of Biochemistry, The University of Hong Kong
"We detected a 4.8-fold increase in the steady-state level of GRP94 in SARS-CoV-infected cells.â
https://www.hkmj.org/abstracts/v15n1s2/37.htm
Cancer-inducible Transgene Expression by the Grp94 Promoter
Spontaneous Activation in Tumors of Various Origins and Cancer-associated Macrophages
Ramachandra K. Reddy, Louis Dubeau, Heather Kleiner, Tyler Parr, Peter Nichols, Bryce Ko, Dezheng Dong, Howard Ko, Changhui Mao, John DiGiovanni and Amy S. Lee
DOI: Published December 2002
Abstract
A major challenge in treating cancer is the difficulty of bringing therapy to poorly perfused areas of solid tumors, which are often most resistant to chemotherapy and radiation. GRP94 is a chaperone protein localized in the endoplasmic reticulum with antiapoptotic properties. We report here that in vitro the proximal murine grp94 promoter is regulated differently from the hypoxia response element fused to the SV40 minimal promoter, with glucose starvation as an inducer of grp94 but a potent repressor of the hypoxia response element/SV40 fusion promoter. Through the use of transgenic mouse models, we showed that LacZ transgene expression driven by the grp94 promoter was strongly activated not only in spontaneous but also in a variety of chemically induced tumors. We additionally discovered that macrophages in the vicinity of malignant tumor showed a high level of transgene expression, consistent with intense β-galactosidase staining at boundaries between viable tumor cells and necrotic areas. Isolated macrophages also showed grp94 mRNA and transgene activation under glucose starvation in vitro. In contrast, transgene activity was not detected in the normal tissue counterparts of any of the malignant tumors examined or macrophages associated with normal organs. These studies provide direct evidence that the tumor microenvironment is a potent physiological inducer of the grp94 promoter. The unique properties of the grp94 promoter suggest that it may offer a novel tool for directing transcription of therapeutic agents to tumors particularly in resistant regions bordering necrotic areas, delivered through standard vectors or macrophages.
https://cancerres.aacrjournals.org/content/62/24/7207
https://twitter.com/N625662/status/1479487582727815173?s=19
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