Evidence map›Paper›PMID 29047390›Full record

ArticleBreast cancer research : BCR2017

Roles of BCCIP deficiency in mammary tumorigenesis.

Roberto Droz-Rosario, Huimei Lu, Jingmei Liu, Ning-Ang Liu, Shridar Ganesan, Bing Xia, Bruce G Haffty, Zhiyuan Shen

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

Article in Breast cancer research : BCR, 2017. 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
1.5field-weighted citation impact, top 19% 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, 22 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

8 authors at 1 institution in 1 country.

Roberto Droz-RosarioRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Huimei LuRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Jingmei LiuRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Ning-Ang LiuRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Shridar GanesanRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Bing XiaRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Bruce G HafftyRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA.
Zhiyuan ShenRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903, USA. shenzh@cinj.rutgers.edu.ORCID http://orcid.org/0000-0003-2834-0309
Rutgers, The State University of New Jersey · US

Funding

TRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Tracie Saunders · 1997 to 2026
$94.5M
Role of PALB2 in the DNA Damage Response and Cancer SuppressionR01CA138804 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI XIA, BING · 2009 to 2024
$5.5M
Molecular modulators of radiation-induced chromosome instability and hematopoietic damageR01CA195612 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI SHEN, ZHIYUAN · 2015 to 2025
$3.6M
Targeting Autophagy in Hereditary Breast CancerR01CA188096 · NCI · RBHS -CANCER INSTITUTE OF NEW JERSEY · PI WHITE, EILEEN P., XIA, BING · 2015 to 2019
$2.4M
Alternative Mechanisms to Inactivate p53 During OncogenesisR01CA156706 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI SHEN, ZHIYUAN · 2011 to 2015
$1.9M
NCI NIH HHS P30 CA072720NCI NIH HHS R01 CA138804NCI NIH HHS R01 CA156706NCI NIH HHS R01 CA188096NCI NIH HHS R01 CA195612
6 · The paper itself

Abstract

backgroundDysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of this study were to determine whether BCCIP deficiency contributes to mammary tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality, and to reveal the mechanistic implications of BCCIP in breast cancer interventions.

methodsWe analyzed the BCCIP protein level in 470 cases of human breast cancer to determine the associations between BCCIP and 53BP1, p53, and subtypes of breast cancer. We further constructed a unique BCCIP knockdown mouse model to determine whether a partial BCCIP deficiency leads to spontaneous breast cancer formation.

resultsWe found that the BCCIP protein level is downregulated in 49% of triple-negative breast cancer and 25% of nontriple-negative breast cancer. The downregulation of BCCIP is mutually exclusive with p53 mutations but concurrent with 53BP1 loss in triple-negative breast cancer. In a K14-Cre-mediated conditional BCCIP knockdown mouse model, we found that BCCIP downregulation causes a formation of benign modules in the mammary glands, resembling the epidermal inclusion cyst of the breast. However, the majority of these benign lesions remain indolent, and only ~ 10% of them evolve into malignant tumors after a long latency. This tumor progression is associated with a loss of 53BP1 and p16 expression. BCCIP knockdown did not alter the latency of mammary tumor formation induced by conditional Trp53 deletion.

conclusionsOur data suggest a confounding role of BCCIP deficiency in modulating breast cancer development by enhancing tumor initiation but hindering progression. Furthermore, secondary genetic alternations may overcome the progression suppression imposed by BCCIP deficiency through a synthetic viability mechanism.

Indexed as

AnimalsBRCA2 ProteinCalcium-Binding ProteinsCarcinogenesisCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p21FemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansMammary Glands, HumanMammary Neoplasms, AnimalMiceNuclear ProteinsTriple Negative Breast NeoplasmsTumor Suppressor p53-Binding Protein 1BCCIP protein, humanBCCIP protein, mouseBRCA2 ProteinCalcium-Binding ProteinsCDKN1A protein, humanCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p21Nuclear ProteinsTP53BP1 protein, humanTP53 protein, humanTumor Suppressor p53-Binding Protein 1Tumor Suppressor Protein p5353BP1BCCIPEpidermal inclusion cyst of the breastp16Suppressor of initiation and requisite for progression (SIRP)Synthetic viability

Identifiers

PMID29047390
PMCPMC5648485
OpenAlexW2766632415

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.