ANDROGENIC REGULATION OF ACYL-COA SYN- THETASE 4 IN BREAST CANCER CELLS

DATTILO, MELINA A.; LOPEZ PAULA; ADLER, EVELYN; BENZO YANINA; BIGI, MARÍA M.; CLAVERO ESTEFANIA; PAZ CRISTINA; PODESTA ERNESTO JORGE; MALOBERTI, PAULA

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

It is known that ACSL4 overexpression is involved in the develop-ment of a very aggressive phenotype in breast and prostate cancer.Androgen receptor (AR) expression or androgenic stimulation de-crease mRNA levels of ACSL4 in prostate cancer cells. However,the effects of androgenic regulation in breast cancer cells have notyet been described. The aim of this work is to study whether AR andandrogens regulate ACSL4 transcription in breast cancer cells. Weobserved that AR mRNA is detected in the slightly aggressive breastcancer cell line MCF-7. In contrast, this expression is not detectablein the very aggressive cell line MDA-MB-231. Bioinformatic analysisperformed with the Genomatix tool and contrasted with the AlggenPromo software, showed one AR element (ARE) in a 1.8 kb frag-ment of the human ACSL4 promoter with a score close to 1. Tran-sient transfection of AR in MDA-MB-231 cell line reduced ACSL41,8 kb promoter activity (p<0.001) as measured by the Nano-Glo®Luciferase Assay System (Promega) and this decrease was trans-lated into decreased ACSL4 mRNA levels (p<0.001), quantifiedby real-time qPCR. Cells treated with 10 nM dihydrotestosterone(DHT) in steroid-free medium, showed a decrease of transcriptionalactivity of the promoter and of ACSL4 mRNA levels, both in MCF-7 cells (p<0.001) and in MDA-MB-231 with ectopic expression ofhuman AR (p<0.001). This effect is not observed in MDA-MB-231cells when they are not transiently transfected with the human AR.These results demonstrate the role of androgens in the expressionof ACSL4 in breast cancer cells and suggest that androgen treat-ment could be a tool to reduce the expression of ACSL4 in breastcancer and thus lay the groundwork for the study of androgen-con-taining hormone therapy for breast cancer.