ArticleBreast cancer research : BCR2022
PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development.
Article in Breast cancer research : BCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Clinical and prognostic significance of parathyroid hormone-related protein in breast cancer: a systematic review and meta-analyses of observational studies in women.Endocrine-related cancer · 2026Pooled it
- Parathyroid hormone-related protein is a therapeutic target in idiopathic pulmonary fibrosis.Signal transduction and targeted therapy · 2026Article
- [Overexpression of parathyroid hormone-like hormone facilitates hepatocellular carcinoma progression and correlates with adverse outcomes].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Deletion of PTHrP nuclear localization sequence and carboxyl terminus leads to lung dysplasia.Scientific reports · 2025Article
- Abaloparatide increases bone mass without affecting growth of bone-disseminated cancer cells.JBMR plus · 2025Article
- Review
- PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR.Breast cancer research : BCR · 2024Article
- Progress in Research on Key Factors Regulating Lactation Initiation in the Mammary Glands of Dairy Cows.Genes · 2023Review
- Re-Evaluating the Role of PTHrP in Breast Cancer.Cancers · 2023Review
- STAT family of transcription factors in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Seminars in cancer biology · 2022Review
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundParathyroid hormone-related protein (PTHrP) is required for embryonic breast development and has important functions during lactation, when it is produced by alveolar epithelial cells and secreted into the maternal circulation to mobilize skeletal calcium used for milk production. PTHrP is also produced by breast cancers, and GWAS studies suggest that it influences breast cancer risk. However, the exact functions of PTHrP in breast cancer biology remain unsettled.
methodsWe developed a tetracycline-regulated, MMTV (mouse mammary tumor virus)-driven model of PTHrP overexpression in mammary epithelial cells (Tet-PTHrP mice) and bred these mice with the MMTV-PyMT (polyoma middle tumor-antigen) breast cancer model to analyze the impact of PTHrP overexpression on normal mammary gland biology and in breast cancer progression.
resultsOverexpression of PTHrP in luminal epithelial cells caused alveolar hyperplasia and secretory differentiation of the mammary epithelium with milk production. This was accompanied by activation of Stat5 and increased expression of E74-like factor-5 (Elf5) as well as a delay in post-lactation involution. In MMTV-PyMT mice, overexpression of PTHrP (Tet-PTHrP;PyMT mice) shortened tumor latency and accelerated tumor growth, ultimately reducing overall survival. Tumors overproducing PTHrP also displayed increased expression of nuclear pSTAT5 and Elf5, increased expression of markers of secretory differentiation and milk constituents, and histologically resembled secretory carcinomas of the breast. Overexpression of PTHrP within cells isolated from tumors, but not PTHrP exogenously added to cell culture media, led to activation of STAT5 and milk protein gene expression. In addition, neither ablating the Type 1 PTH/PTHrP receptor (PTH1R) in epithelial cells nor treating Tet-PTHrP;PyMT mice with an anti-PTH1R antibody prevented secretory differentiation or altered tumor latency. These data suggest that PTHrP acts in a cell-autonomous, intracrine manner. Finally, expression of PTHrP in human breast cancers is associated with expression of genes involved in milk production and STAT5 signaling.
conclusionsOur study suggests that PTHrP promotes pathways leading to secretory differentiation and proliferation in both normal mammary epithelial cells and in breast tumor cells.
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