Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/39741
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dc.contributor.authorSu, Yanrong-
dc.contributor.authorDang, Nhi M. M.-
dc.contributor.authorDepypere, Herman-
dc.contributor.authorSantucci-Pereira, Julia-
dc.contributor.authorGutierrez-Diez, Pedro J. J.-
dc.contributor.authorKanefsky, Joice-
dc.contributor.authorJANSSENS, Jaak-
dc.contributor.authorRusso, Jose-
dc.date.accessioned2023-03-20T13:32:57Z-
dc.date.available2023-03-20T13:32:57Z-
dc.date.issued2023-
dc.date.submitted2023-03-16T11:32:28Z-
dc.identifier.citationEUROPEAN JOURNAL OF CANCER PREVENTION, 32 (2) , p. 126 -138-
dc.identifier.urihttp://hdl.handle.net/1942/39741-
dc.description.abstractBackgroundStrategies 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.-
dc.description.sponsorshipThe authors thank the participants in this trial for their willing contribution to the project. In addition, the authors thank the Biostatistics and Bioinformatics Facility at Fox Chase Cancer Center and Drexel university interns. The authors are grateful to Dr. Eric A. Ross for assisting with statistical analysis. The hCG clinical trial was supported by a grant from Think Pink, Belgium, and ECP to Dr. Depypere H. The RNA-seq study was supported by the Barbara and Joseph Breitman donation, the Flyers wives donation, and the NCI/NIH Cancer Center Support Grant P30-CA006927 to Dr. Russo J. Resources needed for the collaboration of Dr. Gutiérrez-Díez P were financed by the University of Valladolid (Spain) and the Spanish Ministry of Science, grant PID2020-113554GB-I00. The breast tissue biopsies of the patients were obtained from Dr. Herman Depypere at the Ghent University Hospital, after obtaining the consent of the participants and the approval of the ethical board of the Ghent University Hospital in Belgium (EudraCT number: 2015-001720-36; EC number: 2015/0588). All data are provided in the article. The raw RNA-seq data will be available upon a reasonable request to Dr. Herman Depypere. Y.S. received breast biopsy specimens, performed histological analysis, extracted RNA for RNA-seq, conducted qRT-PCR and IHC validation for clinical trial; N. D. Performed RNA-seq analysis and statistical analysis of qRT-PCR. Y.S. and N.D. interpreted data and wrote the article. H. P. conducted the clinical trial, participated in the discussion during the study, and reviewed the article. J.S.-P. assisted the management of the breast biopsy specimens, contributed to the design of clinical trial RNA-seq and RNA preparation for RNA-seq, P.G. performed analysis on GPCR signaling associated genes. J.K. helped with RNA preparation for RNA-seq. J.J. helped in the design and collection of biopsy specimens for the clinical trial, and reviewed the article. J.R. conceived the whole study, designed the clinical trial, received the research funding, supervised the study, and reviewed the article.-
dc.language.isoen-
dc.publisherLIPPINCOTT WILLIAMS & WILKINS-
dc.rights2022 Wolters Kluwer Health, Inc. All rights reserved.-
dc.subject.otherbreast cancer-
dc.subject.othercancer prevention-
dc.subject.otherhuman chorionic gonadotropin-
dc.subject.otherWnt signaling-
dc.subject.otherMYC-
dc.subject.otherTGFB-
dc.subject.otherBRCA1-
dc.subject.otherTP53-
dc.titleRecombinant human chorionic gonadotropin induces signaling pathways towards cancer prevention in the breast of BRCA1/2 mutation carriers-
dc.typeJournal Contribution-
dc.identifier.epage138-
dc.identifier.issue2-
dc.identifier.spage126-
dc.identifier.volume32-
local.format.pages13-
local.bibliographicCitation.jcatA1-
dc.description.notesSu, YR (corresponding author), Fox Chase Canc Ctr Temple Hlth, Irma H Russo MD Breast Canc Res Lab, 333 Cottman Ave, Philadelphia, PA 19111 USA.-
dc.description.notesYanrong.Su@fccc.edu-
local.publisher.placeTWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA-
local.type.refereedRefereed-
local.type.specifiedArticle-
dc.identifier.doi10.1097/CEJ.0000000000000763-
dc.identifier.pmid35881946-
dc.identifier.isi000924066200005-
local.provider.typewosris-
local.description.affiliation[Su, Yanrong; Dang, Nhi M. M.; Santucci-Pereira, Julia; Kanefsky, Joice; Russo, Jose] Fox Chase Canc Ctr Temple Hlth, Irma H Russo MD Breast Canc Res Lab, 333 Cottman Ave, Philadelphia, PA 19111 USA.-
local.description.affiliation[Depypere, Herman] Univ Hosp Ghent, Dept Gynecol, Breast & Menopause Clin, Ghent, Belgium.-
local.description.affiliation[Gutierrez-Diez, Pedro J. J.] Univ Valladolid, IMUVA Math Inst, Valladolid, Spain.-
local.description.affiliation[Janssens, Jaak Ph.] Univ Hasselt, European Canc Prevent Org, Hasselt, Belgium.-
local.uhasselt.internationalyes-
item.fullcitationSu, Yanrong; Dang, Nhi M. M.; Depypere, Herman; Santucci-Pereira, Julia; Gutierrez-Diez, Pedro J. J.; Kanefsky, Joice; JANSSENS, Jaak & Russo, Jose (2023) Recombinant human chorionic gonadotropin induces signaling pathways towards cancer prevention in the breast of BRCA1/2 mutation carriers. In: EUROPEAN JOURNAL OF CANCER PREVENTION, 32 (2) , p. 126 -138.-
item.fulltextWith Fulltext-
item.accessRightsRestricted Access-
item.contributorSu, Yanrong-
item.contributorDang, Nhi M. M.-
item.contributorDepypere, Herman-
item.contributorSantucci-Pereira, Julia-
item.contributorGutierrez-Diez, Pedro J. J.-
item.contributorKanefsky, Joice-
item.contributorJANSSENS, Jaak-
item.contributorRusso, Jose-
crisitem.journal.issn0959-8278-
crisitem.journal.eissn1473-5709-
Appears in Collections:Research publications
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