ArticleCancer research2014
PELP1 overexpression in the mouse mammary gland results in the development of hyperplasia and carcinoma.
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.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- A First-in-Class Inhibitor of ER Coregulator PELP1 Targets ER+ Breast Cancer.Cancer research · 2022Article
- SETDB1 interactions with PELP1 contributes to breast cancer endocrine therapy resistance.Breast cancer research : BCR · 2022Article
- Inflammation-induced PELP1 expression promotes tumorigenesis by activating GM-CSF paracrine secretion in the tumor microenvironment.The Journal of biological chemistry · 2022Article
- Hereditary and breastfeeding factors are positively associated with the aetiology of mammary gland hyperplasia: a case-control study.International health · 2021Article
- Interaction of transcription factor AP-2 gamma with proto-oncogene PELP1 promotes tumorigenesis by enhancing RET signaling.Molecular oncology · 2021Article
- Role of estrogen receptor coregulators in endocrine resistant breast cancer.Exploration of targeted anti-tumor therapy · 2021Article
- PELP1 signaling contributes to medulloblastoma progression by regulating the NF-κB pathway.Molecular carcinogenesis · 2020Article
- Estrogen receptor coregulator binding modulator (ERX-11) enhances the activity of CDK4/6 inhibitors against estrogen receptor-positive breast cancers.Breast cancer research : BCR · 2019Article
- The Clinical Value of PELP1 for Breast Cancer: A Comparison with Multiple Cancers and Analysis in Breast Cancer Subtypes.Cancer research and treatment · 2019Article
- PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway.Frontiers in oncology · 2019Article
- Cancer Stem Cell Phenotypes in ERMolecular cancer research : MCR · 2018Article
- PELP1: a key mediator of oestrogen signalling and actions in the brain.Journal of neuroendocrinology · 2018Review
- Article
- Cytoplasmic Localization of Proline, Glutamic Acid, Leucine-rich Protein 1 (PELP1) Induces Breast Epithelial Cell Migration through Up-regulation of Inhibitor of κB Kinase ϵ and Inflammatory Cross-talk with Macrophages.The Journal of biological chemistry · 2017Article
- Review
- Article
- PELP1 promotes glioblastoma progression by enhancing Wnt/β-catenin signaling.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
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.