Drivers and suppressors of triple-negative breast cancer.
Amphibian Proteins
/ genetics
Animals
Benzopyrans
/ pharmacology
Calcitriol
/ pharmacology
Cytochrome P-450 Enzyme System
/ genetics
Down-Regulation
Estrogen Receptor alpha
/ genetics
Estrogen Receptor beta
/ genetics
Fatty Acids
/ metabolism
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Mice
Neoplasms, Experimental
Random Allocation
Survivin
/ genetics
Transcriptome
Tretinoin
/ pharmacology
Triple Negative Breast Neoplasms
/ genetics
Wnt Proteins
/ genetics
breast cancer
cytochrome P450
estrogen receptor beta
fatty acid oxidation
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
17 08 2021
17 08 2021
Historique:
entrez:
14
8
2021
pubmed:
15
8
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor β (ERβ) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERβ. ERβ is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERβ
Identifiants
pubmed: 34389675
pii: 2104162118
doi: 10.1073/pnas.2104162118
pmc: PMC8379974
pii:
doi:
Substances chimiques
Amphibian Proteins
0
BIRC5 protein, human
0
Benzopyrans
0
Estrogen Receptor alpha
0
Estrogen Receptor beta
0
Fatty Acids
0
Survivin
0
Wnt Proteins
0
Wnt-10a protein, Pleurodeles waltl
0
erteberel
2ZUL6758TZ
Tretinoin
5688UTC01R
Cytochrome P-450 Enzyme System
9035-51-2
Calcitriol
FXC9231JVH
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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