Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR)

Abujiang Pataer; Stephan A. Vorburger; Glen N. Barber; Sunil Chada; Abner M. Mhashilkar; Helena Zou-Yang; Alexis L. Stewart; Siddharth Balachandran; Jack A. Roth; Kelly K. Hunt; Stephen G. Swisher

Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR)

Abujiang Pataer
, Stephan A. Vorburger
, Glen N. Barber
, Sunil Chada
, Abner M. Mhashilkar
, Helena Zou-Yang
, Alexis L. Stewart
, Siddharth Balachandran
, Jack A. Roth
, Kelly K. Hunt
, Stephen G. Swisher

University of Texas MD Anderson Cancer Center
University of Miami
Introgen Therapeutics Inc.

Research output: Contribution to journal › Article › peer-review

142 Scopus citations

Abstract

Adenoviral-mediated overexpression of the melanoma differentiation-associated gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although the mechanism is not well understood. We report that Ad-mda7 induces and activates the double-stranded RNA-dependent protein kinase (PKR), which leads to phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF-2α) and the induction of apoptosis in lung cancer cells. Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2α phosphorylation, and apoptosis induction by Ad-mda7. Additionally, PKR null but not wild-type fibroblasts are resistant to Ad-mda7-induced apoptosis. These results suggest that the activation of PKR and its downstream targets may be a critical pathway for Ad-mda7-mediated apoptosis.

Original language	English
Pages (from-to)	2239-2243
Number of pages	5
Journal	Cancer Research
Volume	62
Issue number	8
State	Published - Apr 15 2002

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

2-Aminopurine/pharmacology
Adenoviridae/genetics
Apoptosis/genetics
DNA-Binding Proteins/metabolism
Enzyme Induction
Enzyme Inhibitors/pharmacology
Gene Transfer Techniques
Genes, Tumor Suppressor
Growth Substances/genetics
Humans
Interleukins
Lung Neoplasms/enzymology
Phosphorylation
Transcription Factors/metabolism
Tumor Cells, Cultured
Up-Regulation
eIF-2 Kinase/antagonists & inhibitors

Cite this

Pataer, A., Vorburger, S. A., Barber, G. N., Chada, S., Mhashilkar, A. M., Zou-Yang, H., Stewart, A. L., Balachandran, S., Roth, J. A., Hunt, K. K., & Swisher, S. G. (2002). Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR). Cancer Research, 62(8), 2239-2243.

@article{b43184271b484c8b94312d89c145aa81,

title = "Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR)",

abstract = "Adenoviral-mediated overexpression of the melanoma differentiation-associated gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although the mechanism is not well understood. We report that Ad-mda7 induces and activates the double-stranded RNA-dependent protein kinase (PKR), which leads to phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF-2α) and the induction of apoptosis in lung cancer cells. Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2α phosphorylation, and apoptosis induction by Ad-mda7. Additionally, PKR null but not wild-type fibroblasts are resistant to Ad-mda7-induced apoptosis. These results suggest that the activation of PKR and its downstream targets may be a critical pathway for Ad-mda7-mediated apoptosis.",

keywords = "2-Aminopurine/pharmacology, Adenoviridae/genetics, Apoptosis/genetics, DNA-Binding Proteins/metabolism, Enzyme Induction, Enzyme Inhibitors/pharmacology, Gene Transfer Techniques, Genes, Tumor Suppressor, Growth Substances/genetics, Humans, Interleukins, Lung Neoplasms/enzymology, Phosphorylation, Transcription Factors/metabolism, Tumor Cells, Cultured, Up-Regulation, eIF-2 Kinase/antagonists \& inhibitors",

author = "Abujiang Pataer and Vorburger, \{Stephan A.\} and Barber, \{Glen N.\} and Sunil Chada and Mhashilkar, \{Abner M.\} and Helena Zou-Yang and Stewart, \{Alexis L.\} and Siddharth Balachandran and Roth, \{Jack A.\} and Hunt, \{Kelly K.\} and Swisher, \{Stephen G.\}",

year = "2002",

month = apr,

day = "15",

language = "English",

volume = "62",

pages = "2239--2243",

journal = "Cancer Research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

number = "8",

}

Pataer, A, Vorburger, SA, Barber, GN, Chada, S, Mhashilkar, AM, Zou-Yang, H, Stewart, AL, Balachandran, S, Roth, JA, Hunt, KK & Swisher, SG 2002, 'Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR)', Cancer Research, vol. 62, no. 8, pp. 2239-2243.

Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR). / Pataer, Abujiang; Vorburger, Stephan A.; Barber, Glen N. et al.
In: Cancer Research, Vol. 62, No. 8, 15.04.2002, p. 2239-2243.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR)

AU - Pataer, Abujiang

AU - Vorburger, Stephan A.

AU - Barber, Glen N.

AU - Chada, Sunil

AU - Mhashilkar, Abner M.

AU - Zou-Yang, Helena

AU - Stewart, Alexis L.

AU - Balachandran, Siddharth

AU - Roth, Jack A.

AU - Hunt, Kelly K.

AU - Swisher, Stephen G.

PY - 2002/4/15

Y1 - 2002/4/15

N2 - Adenoviral-mediated overexpression of the melanoma differentiation-associated gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although the mechanism is not well understood. We report that Ad-mda7 induces and activates the double-stranded RNA-dependent protein kinase (PKR), which leads to phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF-2α) and the induction of apoptosis in lung cancer cells. Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2α phosphorylation, and apoptosis induction by Ad-mda7. Additionally, PKR null but not wild-type fibroblasts are resistant to Ad-mda7-induced apoptosis. These results suggest that the activation of PKR and its downstream targets may be a critical pathway for Ad-mda7-mediated apoptosis.

AB - Adenoviral-mediated overexpression of the melanoma differentiation-associated gene 7 (Ad-mda7) induces apoptosis in a wide range of cancer cells, although the mechanism is not well understood. We report that Ad-mda7 induces and activates the double-stranded RNA-dependent protein kinase (PKR), which leads to phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF-2α) and the induction of apoptosis in lung cancer cells. Treatment with 2-aminopurine (2-AP), a serine/threonine kinase inhibitor, inhibits PKR activation, eIF2α phosphorylation, and apoptosis induction by Ad-mda7. Additionally, PKR null but not wild-type fibroblasts are resistant to Ad-mda7-induced apoptosis. These results suggest that the activation of PKR and its downstream targets may be a critical pathway for Ad-mda7-mediated apoptosis.

KW - 2-Aminopurine/pharmacology

KW - Adenoviridae/genetics

KW - Apoptosis/genetics

KW - DNA-Binding Proteins/metabolism

KW - Enzyme Induction

KW - Enzyme Inhibitors/pharmacology

KW - Gene Transfer Techniques

KW - Genes, Tumor Suppressor

KW - Growth Substances/genetics

KW - Humans

KW - Interleukins

KW - Lung Neoplasms/enzymology

KW - Phosphorylation

KW - Transcription Factors/metabolism

KW - Tumor Cells, Cultured

KW - Up-Regulation

KW - eIF-2 Kinase/antagonists & inhibitors

UR - https://www.scopus.com/pages/publications/0037089491

M3 - Article

C2 - 11956076

AN - SCOPUS:0037089491

SN - 0008-5472

VL - 62

SP - 2239

EP - 2243

JO - Cancer Research

JF - Cancer Research

IS - 8

ER -

Adenoviral transfer of the melanoma differentiation-associated gene 7 (mda7) induces apoptosis of lung cancer cells via up-regulation of the double-stranded RNA-dependent protein kinase (PKR)

Abstract

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Keywords

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