Evidence map›Paper›PMID 25377474›Full record

ArticleCancer research2014

PELP1 overexpression in the mouse mammary gland results in the development of hyperplasia and carcinoma.

Valerie Cortez, Cathy Samayoa, Andrea Zamora, Lizatte Martinez, Rajeshwar R Tekmal, Ratna K Vadlamudi

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 27 citations in OpenAlex.

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  11. Cancer Stem Cell Phenotypes in ERMolecular cancer research : MCR · 2018
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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

6 authors at 1 institution in 1 country.

Valerie CortezDepartment of Obstetrics and Gynecology, UT Health Science Center, San Antonio, Texas. Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, Texas.
Cathy SamayoaDepartment of Obstetrics and Gynecology, UT Health Science Center, San Antonio, Texas. Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, Texas.
Andrea ZamoraDepartment of Obstetrics and Gynecology, UT Health Science Center, San Antonio, Texas.
Lizatte MartinezDepartment of Obstetrics and Gynecology, UT Health Science Center, San Antonio, Texas.
Rajeshwar R TekmalDepartment of Obstetrics and Gynecology, UT Health Science Center, San Antonio, Texas. Cancer Therapy and Research Center, UT Health Science Center, San Antonio, Texas.
Ratna K VadlamudiDepartment of Obstetrics and Gynecology, UT Health Science Center, San Antonio, Texas. Cancer Therapy and Research Center, UT Health Science Center, San Antonio, Texas. vadlamudi@uthscsa.edu.
The University of Texas Health Science Center at San Antonio · US

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
PELP1, a Novel Regulator of Estrogen ReceptorR01CA095681 · NCI · UNIVERSITY OF TEXAS MD ANDERSON CAN CTR · PI VADLAMUDI, RATNA K · 2003 to 2013
$2.5M
Significance of PELP1 in Breast Cancer ProgressionF31CA165814 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI CORTEZ, VALERIE ANN · 2011 to 2013
$56k
NCI NIH HHS CA095681NCI NIH HHS F31CA165814NCI NIH HHS P30 CA054174NCI NIH HHS P30CA054174-17NCI NIH HHS R01 CA095681
6 · The paper itself

Abstract

Estrogen receptor (ER) coregulator overexpression promotes carcinogenesis and/or progression of endocrine related-cancers in which steroid hormones are powerful mitogenic agents. Recent studies in our laboratory, as well as others, demonstrated that the estrogen receptor coregulator PELP1 is a proto-oncogene. PELP1 interactions with histone demethylase KDM1 play a critical role in its oncogenic functions and PELP1 is a prognostic indicator of decreased survival in patients with breast cancer. However, the in vivo significance of PELP1 deregulation during initiation and progression of breast cancer remains unknown. We generated an inducible, mammary gland-specific PELP1-expressing transgenic (Tg) mouse (MMTVrtTA-TetOPELP1). We found more proliferation, extensive side branching, and precocious differentiation in PELP1-overexpressing mammary glands than in control glands. Aged MMTVrtTA-TetOPELP1 Tg mice had hyperplasia and preneoplastic changes as early as 12 weeks, and ER-positive mammary tumors occurred at a latency of 14 to 16 months. Mechanistic studies revealed that PELP1 deregulation altered expression of a number of known ER target genes involved in cellular proliferation (cyclin D1, CDKs) and morphogenesis (EGFR, MMPs) and such changes facilitated altered mammary gland morphogenesis and tumor progression. Furthermore, PELP1 was hyper-phosphorylated at its CDK phosphorylation site, suggesting an autocrine loop involving the CDK-cyclin D1-PELP1 axis in promoting mammary tumorigenesis. Treatment of PELP1 Tg mice with a KDM1 inhibitor significantly reduced PELP1-driven hyperbranching, reversed alterations in cyclin D1 expression levels, and reduced CDK-driven PELP1 phosphorylation. These results further support the hypothesis that PELP1 deregulation has the potential to promote breast tumorigenesis in vivo and represent a novel model for future investigation into molecular mechanisms of PELP1-mediated tumorigenesis.

Indexed as

AnimalsBreast NeoplasmsCarcinomaCell ProliferationCo-Repressor ProteinsCyclin-Dependent KinasesEstrogen Receptor alphaFemaleGene Expression Regulation, NeoplasticHumansHyperplasiaMammary Glands, AnimalMiceMice, TransgenicProto-Oncogene MasTranscription FactorsCo-Repressor ProteinsCyclin-Dependent KinasesESR1 protein, humanEstrogen Receptor alphaMAS1 protein, humanPELP1 protein, humanProto-Oncogene MasTranscription Factors

Identifiers

PMID25377474
PMCPMC4268231
OpenAlexW1977781463

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.