Evidence map›Paper›PMID 30611295›Full record

ArticleBreast cancer research : BCR2019

A method of producing genetically manipulated mouse mammary gland.

Hiroaki Tagaya, Kosuke Ishikawa, Yoshito Hosokawa, Shun Kobayashi, Yukino Ueoka, Mayuna Shimada, Yasuko Ohashi, Hirofumi Mikami, Mizuki Yamamoto, Tatsuya Ihara and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
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

6 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Sonogenetics in the Treatment of Chronic Diseases: A New Method for Cell Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review
  3. Review
  4. Article
  5. Pharmaceutics · 2020
    Review
  6. Article
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

15 authors at 4 institutions in 1 country.

Hiroaki TagayaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Kosuke IshikawaJapan Biological Informatics Consortium (JBiC), 2-45 Aomi, Koto-ku, Tokyo, 135-8073, Japan. ishikawakosuke@gmail.com.ORCID 0000-0001-8339-1075
Yoshito HosokawaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Shun KobayashiDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Yukino UeokaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Mayuna ShimadaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Yasuko OhashiDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Hirofumi MikamiDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Mizuki YamamotoDivision of Cellular and Molecular Biology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Tatsuya IharaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Kentaro KumazawaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Kosuke SugiharaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
Naoki GoshimaNational Institute of Advanced Industrial Science and Technology (AIST), Koto-ku, Tokyo, 135-0064, Japan.
Shinya WatanabeTranslational Research Center, Fukushima Medical University, Hikarigaoka, Fukushima, 960-1295, Japan.
Kentaro SembaDepartment of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan. ksemba@waseda.jp.
Waseda University · JPFukushima Medical University · JPJapan Biological Informatics Consortium · JPThe University of Tokyo · JP

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundTo obtain a deep understanding of the mechanism by which breast cancer develops, the genes involved in tumorigenesis should be analyzed in vivo. Mouse mammary gland can regenerate completely from a mammary stem cell (MaSC), which enables us to analyze the effect of gene expression and repression on tumorigenesis in mammary gland regenerated from genetically manipulated MaSCs. Although lentiviral and retroviral systems have usually been applied for gene transduction into MaSCs, they are associated with difficulty in introducing long, repeated, or transcriptional termination sequences. There is thus a need for an easier and quicker gene delivery system.

methodsWe devised a new system for gene delivery into MaSCs using the piggyBac transposon vectors and electroporation. Compared with viral systems, this system enables easier and quicker transfection of even long, repeated, or transcriptional termination DNA sequences. We designed gene expression vectors of the transposon system, equipped with a luciferase (Luc) expression cassette for monitoring gene transduction into regenerative mammary gland in mice by in-vivo imaging. A doxycycline (Dox)-inducible system was also integrated for expressing the target gene after mammary regeneration to mimic the actual mechanism of tumorigenesis.

resultsWith this new gene delivery system, genetically manipulated mammary glands were successfully reconstituted even though the vector size was > 200 kb and even in the presence of DNA elements such as promoters and transcription termination sequences, which are major obstacles to viral vector packaging. They differentiated correctly into both basal and luminal cells, and showed normal morphological change and milk production after pregnancy, as well as self-renewal capacity. Using the Tet-On system, gene expression can be controlled by the addition of Dox after mammary reconstitution. In a case study using polyoma-virus middle T antigen (PyMT), oncogene-induced tumorigenesis was achieved. The histological appearance of the tumor was highly similar to that of the mouse mammary tumor virus-PyMT transgenic mouse model.

conclusionsWith this system, gene transduction in the mammary gland can be easily and quickly achieved, and gene expression can be controlled by Dox administration. This system for genetic manipulation could be useful for analyzing genes involved in breast cancer.

Indexed as

AnimalsCell DifferentiationCell LineDNA-Binding ProteinsDNA Transposable ElementsDoxycyclineFemaleFibroblastsGene Expression RegulationGenes, ReporterGenetic EngineeringGenetic VectorsGreen Fluorescent ProteinsMammary Glands, AnimalMammary Neoplasms, ExperimentalMiceDNA-Binding ProteinsDNA Transposable ElementsDoxycyclineGreen Fluorescent ProteinsRag2 protein, mouseDoxycyclineElectroporationMaSCPiggyBacTet-On systemTransgenesisTransposon

Identifiers

PMID30611295
PMCPMC6321679
OpenAlexW2911284107

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.