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Title: | Recombinant human chorionic gonadotropin induces signaling pathways towards cancer prevention in the breast of BRCA1/2 mutation carriers | Authors: | Su, Yanrong Dang, Nhi M. M. Depypere, Herman Santucci-Pereira, Julia Gutierrez-Diez, Pedro J. J. Kanefsky, Joice JANSSENS, Jaak Russo, Jose |
Issue Date: | 2023 | Publisher: | LIPPINCOTT WILLIAMS & WILKINS | Source: | EUROPEAN JOURNAL OF CANCER PREVENTION, 32 (2) , p. 126 -138 | Abstract: | BackgroundStrategies for breast cancer prevention in women with germline BRCA1/2 mutations are limited. We previously showed that recombinant human chorionic gonadotropin (r-hCG) induces mammary gland differentiation and inhibits mammary tumorigenesis in rats. The present study investigated hCG-induced signaling pathways in the breast of young nulliparous women carrying germline BRCA1/2 mutations. MethodsWe performed RNA-sequencing on breast tissues from 25 BRCA1/2 mutation carriers who received r-hCG treatment for 3 months in a phase II clinical trial, we analyzed the biological processes, reactome pathways, canonical pathways, and upstream regulators associated with genes differentially expressed after r-hCG treatment, and validated genes of interest. ResultsWe observed that r-hCG induces remarkable transcriptomic changes in the breast of BRCA1/2 carriers, especially in genes related to cell development, cell differentiation, cell cycle, apoptosis, DNA repair, chromatin remodeling, and G protein-coupled receptor signaling. We revealed that r-hCG inhibits Wnt/beta-catenin signaling, MYC, HMGA1, and HOTAIR, whereas activates TGFB/TGFBR-SMAD2/3/4, BRCA1, TP53, and upregulates BRCA1 protein. ConclusionOur data suggest that the use of r-hCG at young age may reduce the risk of breast cancer in BRCA1/2 carriers by inhibiting pathways associated with stem/progenitor cell maintenance and neoplastic transformation, whereas activating genes crucial for breast epithelial differentiation and lineage commitment, and DNA repair. | Notes: | Su, YR (corresponding author), Fox Chase Canc Ctr Temple Hlth, Irma H Russo MD Breast Canc Res Lab, 333 Cottman Ave, Philadelphia, PA 19111 USA. Yanrong.Su@fccc.edu |
Keywords: | breast cancer;cancer prevention;human chorionic gonadotropin;Wnt signaling;MYC;TGFB;BRCA1;TP53 | Document URI: | http://hdl.handle.net/1942/39741 | ISSN: | 0959-8278 | e-ISSN: | 1473-5709 | DOI: | 10.1097/CEJ.0000000000000763 | ISI #: | 000924066200005 | Rights: | 2022 Wolters Kluwer Health, Inc. All rights reserved. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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