Evidence map›Paper›PMID 23376849›Full record

ArticleOncogene2014

Ink4a/Arf(-/-) and HRAS(G12V) transform mouse mammary cells into triple-negative breast cancer containing tumorigenic CD49f(-) quiescent cells.

K Kai, T Iwamoto, T Kobayashi, Y Arima, Y Takamoto, N Ohnishi, C Bartholomeusz, R Horii, F Akiyama, G N Hortobagyi and 3 more

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

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

5 citing papers in PubMed, 11 citations in OpenAlex.

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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 at 3 institutions in 2 countries.

K Kai1] Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [3] Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
T IwamotoDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
T KobayashiDivision of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
Y ArimaDivision of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
Y TakamotoDivision of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
N OhnishiDivision of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
C Bartholomeusz1] Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
R HoriiDivision of Pathology, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
F AkiyamaDivision of Pathology, The Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.
G N HortobagyiDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
L Pusztai1] Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
H SayaDivision of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo, Japan.
N T Ueno1] Breast Cancer Translational Research Laboratory, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · USKeio University · JPJapanese Foundation For Cancer Research · JP

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Markers of sensivity to the EGFR inhibitor erlotinib in breast cancerR01CA123318 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI UENO, NAOTO T. · 2007 to 2012
$1.4M
NCI NIH HHS 5 P30 CA016672-36NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA123318NCI NIH HHS R01 CA123318-01A1
6 · The paper itself

Abstract

Intratumoral heterogeneity within individual breast tumors is a well-known phenomenon that may contribute to drug resistance. This heterogeneity is dependent on several factors, such as types of oncogenic drivers and tumor precursor cells. The purpose of our study was to engineer a mouse mammary tumor model with intratumoral heterogeneity by using defined genetic perturbations. To achieve this, we used mice with knockout (-/-) of Ink4a/Arf, a tumor suppressor locus; these mice are known to be susceptible to non-mammary tumors such as fibrosarcoma. To induce mammary tumors, we retrovirally introduced an oncogene, HRAS(G12V), into Ink4a/Arf(-/-) mammary cells in vitro, and those cells were inoculated into syngeneic mice mammary fat pads. We observed 100% tumorigenesis. The tumors formed were negative for estrogen receptor, progesterone receptor and HER2. Further, they had pathological features similar to those of human triple-negative breast cancer (TNBC) (for example, pushing borders, central necrosis). The tumors were found to be heterogeneous and included two subpopulations: CD49f(-) quiescent cells and CD49f(+)cells. Contrary to our expectation, CD49f(-) quiescent cells had high tumor-initiating potential and CD49f(+)cells had relatively low tumor-initiating potential. Gene expression analysis revealed that CD49f(-) quiescent cells overexpressed epithelial-to-mesenchymal transition-driving genes, reminiscent of tumor-initiating cells and claudin-low breast cancer. Our animal model with intratumoral heterogeneity, derived from defined genetic perturbations, allows us to test novel molecular targeted drugs in a setting that mimics the intratumoral heterogeneity of human TNBC.

Indexed as

AnimalsCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p16FemaleFlow CytometryImmunohistochemistryIntegrin alpha6Mammary Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, KnockoutNeoplastic Stem CellsOligonucleotide Array Sequence AnalysisProto-Oncogene Proteins p21(ras)Real-Time Polymerase Chain ReactionTriple Negative Breast NeoplasmsCyclin-Dependent Kinase Inhibitor p16Hras protein, mouseIntegrin alpha6Proto-Oncogene Proteins p21(ras)

Identifiers

PMID23376849
PMCPMC3957346
OpenAlexW2090347939

What Socratic holds

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LicenceTDM
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 Socratic graph.