Evidence map›Paper›PMID 35326649›Full record

ArticleCancers2022

Conversion of a Non-Cancer-Selective Promoter into a Cancer-Selective Promoter.

Praveen Bhoopathi, Anjan K Pradhan, Amit Kumar, Santanu Maji, Padmanabhan Mannangatti, Xiaoyan Deng, Dipankar Bandyopadhyay, Devanand Sarkar, Xiang-Yang Wang, Joseph W Landry and 3 more

Abstract read
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In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Praveen BhoopathiDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Anjan K PradhanDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Amit KumarDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-3079-2067
Santanu MajiDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Padmanabhan MannangattiDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Xiaoyan DengDepartment of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Dipankar BandyopadhyayDepartment of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Devanand SarkarDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-0973-2323
Xiang-Yang WangDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Joseph W LandryDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Swadesh K DasDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Luni EmdadDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Paul B FisherDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
Novel Targeted Combinatorial Therapy for Hepatocellular CarcinomaR01CA244993 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B, SARKAR, DEVANAND · 2020 to 2024
$2.7M
Interplay between tumor and microenvironment in bone metastasisR01CA259599 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B, WANG, XIANG-YANG SHAWN · 2021 to 2025
$2.3M
National Foundation for Cancer Research N/ANCI NIH HHS P30 CA016059NCI NIH HHS R01 CA244993NIH HHS CA016059NIH HHS CA244993NIH HHS CA259599Sponsored research agreement between InterLeukin Combinatorial Therapies and VCU SOM N/AUnited States Department of Defense W81XWH-19-1-0489
6 · The paper itself

Abstract

Progression-elevated gene-3 (PEG-3) and rat growth arrest and DNA damage-inducible gene-34 (GADD34) display significant sequence homology with regulation predominantly transcriptional. The rat full-length (FL) and minimal (min) PEG-3 promoter display cancer-selective expression in rodent and human tumors, allowing for cancer-directed regulation of transgenes, viral replication and in vivo imaging of tumors and metastases in animals, whereas the FL- and min-GADD34-Prom lack cancer specificity. Min-PEG-Prom and min-GADD34-Prom have identical sequences except for two single-point mutation differences (at -260 bp and +159 bp). Engineering double mutations in the min-GADD34-Prom produce the GAPE-Prom. Changing one base pair (+159) or both point mutations in the min-GADD34-Prom, but not the FL-GADD34-Prom, results in cancer-selective transgene expression in diverse cancer cells (including prostate, breast, pancreatic and neuroblastoma) vs. normal counterparts. Additionally, we identified a GATA2 transcription factor binding site, promoting cancer specificity when both min-PEG-Prom mutations are present in the GAPE-Prom. Taken together, introducing specific point mutations in a rat min-GADD34-Prom converts this non-cancer-specific promoter into a cancer-selective promoter, and the addition of GATA2 with existing AP1 and PEA3 transcription factors enhances further cancer-selective activity of the GAPE-Prom. The GAPE-Prom provides a genetic tool to specifically regulate transgene expression in cancer cells.

Indexed as

cancer selective promoterGADD34GATA2PEG-3transcriptional regulationtumor and metastasis imaging

Identifiers

PMID35326649
PMCPMC8946048

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.