ArticleBreast cancer research and treatment2021
Genetic ablation of pregnancy zone protein promotes breast cancer progression by activating TGF-β/SMAD signaling.
Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
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4 citing papers in PubMed, 8 citations in OpenAlex.
- Development of predictive models for the prognosis of triple-negative breast cancer using multiple transcriptomic analyses.PloS one · 2026Article
- Article
- Pregnancy Zone Protein Serves as a Prognostic Marker and Favors Immune Infiltration in Lung Adenocarcinoma.Biomedicines · 2023Article
- Hepatokine Pregnancy Zone Protein Governs the Diet-Induced Thermogenesis Through Activating Brown Adipose Tissue.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
purposePregnancy zone protein (PZP) is best known as protease inhibitor and its concentration in human blood plasma increases dramatically during pregnancy. Recent investigation revealed a role of PZP inactivating germ-line mutation in breast cancer predisposition, and therefore we designed a study to evaluate functional involvement of this protein in tumor pathogenesis.
methodsPZP knockout cells were generated utilizing the CRISPR-Cas9 approach in MCF7 and T47D (breast cancer) cell lines, and colony formation, cell proliferation, and migration assays carried out. TGF-β and SMAD expression studies were performed using qRT-PCR and Western blot. PZP expression in tumor vs normal tissue was compared using meta-analyses of data records of breast cancer patients (n = 1211) included in the TCGA consortium registry as well as in independent cohorts of hormone receptor-positive (n = 118) and triple-negative breast cancer (TNBC) patients (n = 116).
resultsWe demonstrated that genetic ablation of PZP efficiently inhibits tamoxifen-induced apoptosis and enhances cell proliferation, migration, and colony-forming capacity. We found a significant increase in survival fraction of CRISPR/Cas9-mediated PZP knockout clones compared to wild-type counterpart after tamoxifen treatment (p < 0.05). The PZP knockout significantly promoted breast cancer cell migration (p < 0.01) in vitro. We observed high expression of TGF-β2 ligand, TGF-β- receptor 2, and upregulation of phosphorylated regulatory-SMADs (pSMAD2 and pSMAD3) activating the pro-survival function of TGF-β/SMAD signaling in PZP knockout clones. Meta-analyses of data records of breast cancer patients indicated that low PZP expression is associated with poor overall survival at 6 years (51.7% vs 62.9% in low vs high expressers, respectively; p = 0.026). We also observed a significantly lower PZP mRNA expression in TNBC as compared with hormone receptor-positive tumors (p = 0.019).
conclusionTaken together, our results suggest that genetic ablation of PZP results in tumor progression and low expression of PZP is associated with poor survival of breast cancer patients.
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