ArticleBreast cancer research : BCR2012
Deficiency of the p53/p63 target Perp alters mammary gland homeostasis and promotes cancer.
Article in Breast cancer research : BCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- MiR-125b-5p promotes pemphigus vulgaris pathogenesis by modulating desmosome structures.Bioscience reports · 2026Article
- Perp Deficiency Induces Defective Negative Selection and Autoimmune Arthritis in Aged Mice.Aging cell · 2026Article
- PERP suppresses breast cancer metastasis via the ATF3-HSPA6 signaling pathway.The Journal of international medical research · 2025Article
- N6-Methyladenosine Modification of PERP by RBM15 Enhances the Tumorigenesis of Lung Adenocarcinoma via p53 Signaling Pathway.Molecular biotechnology · 2025Article
- Integrative modeling of malignant epithelial programs in EGFR-mutant LUAD via single-cell transcriptomics and multi-algorithm machine learning.Frontiers in immunology · 2025Article
- DCAF13 promotes breast cancer cell proliferation by ubiquitin inhibiting PERP expression.Cancer science · 2022Article
- The 40bp Indel Polymorphism rs150550023 in theCancers · 2020Article
- Upregulation of METTL14 mediates the elevation of PERP mRNA NMolecular cancer · 2020Article
- Loss ofFrontiers in immunology · 2018Article
- Elucidating the Role of the Desmosome Protein p53 Apoptosis Effector Related to PMP-22 in Growth Hormone Tumors.Endocrinology · 2017Article
- Transcriptomic comparison of primary bovine horn core carcinoma culture and parental tissue at early stage.Veterinary world · 2017Article
- ErbB2-dependent downregulation of a pro-apoptotic protein Perp is required for oncogenic transformation of breast epithelial cells.Oncogene · 2016Article
- Desmosomes in acquired disease.Cell and tissue research · 2015Review
- ALCAM is indirectly modulated by miR-125b in MCF7 cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Transmembrane protein PERP is a component of tessellate junctions and of other junctional and non-junctional plasma membrane regions in diverse epithelial and epithelium-derived cells.Cell and tissue research · 2013Article
- Caspase-1 is a novel target of p63 in tumor suppression.Cell death & disease · 2013Article
- Loss of the p53/p63 target PERP is an early event in oral carcinogenesis and correlates with higher rate of local relapse.Oral surgery, oral medicine, oral pathology and oral radiology · 2013Article
- Structure, function, and regulation of desmosomes.Progress in molecular biology and translational science · 2013Review
- Article
- Downregulation of Hlx closely related to the decreased expressions of T-bet and Runx3 in patients with gastric cancer may be associated with a pathological event leading to the imbalance of Th1/Th2.Clinical & developmental immunology · 2012Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
introductionPerp is a transcriptional target of both p53 during DNA damage-induced apoptosis and p63 during stratified epithelial development. Perp-/- mice exhibit postnatal lethality associated with dramatic blistering of the epidermis and oral mucosa, reflecting a critical role in desmosome-mediated intercellular adhesion in keratinocytes. However, the role of Perp in tissue homeostasis in other p63-dependent stratified epithelial tissues is poorly understood. Given that p63 is essential for proper mammary gland development and that cell adhesion is fundamental for ensuring the proper architecture and function of the mammary epithelium, here we investigate Perp function in the mammary gland.
methodsImmunofluorescence and Western blot analysis were performed to characterize Perp expression and localization in the mouse mammary epithelium throughout development. The consequences of Perp deficiency for mammary epithelial development and homeostasis were examined by using in vivo mammary transplant assays. Perp protein levels in a variety of human breast cancer cell lines were compared with those in untransformed cells with Western blot analysis. The role of Perp in mouse mammary tumorigenesis was investigated by aging cohorts of K14-Cre/+;p53fl/fl mice that were wild-type or deficient for Perp. Mammary tumor latency was analyzed, and tumor-free survival was assessed using Kaplan-Meier analysis.
resultsWe show that Perp protein is expressed in the mammary epithelium, where it colocalizes with desmosomes. Interestingly, although altering desmosomes through genetic inactivation of Perp does not dramatically impair mammary gland ductal development, Perp loss affects mammary epithelial homeostasis by causing the accumulation of inflammatory cells around mature mammary epithelium. Moreover, we show reduced Perp expression in many human breast cancer cell lines compared with untransformed cells. Importantly, Perp deficiency also promotes the development of mouse mammary cancer.
conclusionsTogether, these observations demonstrate an important role for Perp in normal mammary tissue function and in mammary cancer suppression. In addition, our findings highlight the importance of desmosomes in cancer suppression and suggest the merit of evaluating Perp as a potential prognostic indicator or molecular target in breast cancer therapy.
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