Recombinant human chorionic gonadotropin induces signaling pathways towards cancer prevention in the breast of BRCA1/2 mutation carriers.
Eur J Cancer Prev
; 32(2): 126-138, 2023 03 01.
Article
in En
| MEDLINE
| ID: mdl-35881946
ABSTRACT
BACKGROUND:
Strategies 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.METHODS:
We 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.RESULTS:
We 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/ß-catenin signaling, MYC, HMGA1 , and HOTAIR , whereas activates TGFB/TGFBR-SMAD2/3/4, BRCA1, TP53, and upregulates BRCA1 protein.CONCLUSION:
Our 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast
/
Breast Neoplasms
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Eur J Cancer Prev
Journal subject:
NEOPLASIAS
/
SAUDE PUBLICA
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos