CHARACTERIZATION OF R-SPONDIN3 GENE EXPRESSION REGULATION IN HUMAN BREAST CANCER CELLS

ANA LAURA ORTIZ; CARLA FELCHER; PEDRO SALABERRY ; EDITH C. KORDON

Mar del Plata

Congreso; Reunión Anual SAIC 2023; 2023

SAIC

We have determined that R-spondin3 (RSPO3), a secreted proteinthat potentiates Wnt signaling pathway, is a key modulator of tumorprogression and stem cell behavior in basal-like breast cancer(BL-BC) cells. Although the highest RSPO3 expression has beendetected in cells of this cancer subtype, immunohistochemicalanalysis showed that a high proportion of human breast luminaltumors are positive for RSPO3. We have also found that blockingRUNX-CBFβ activity inhibited RSPO3 expression in the BL-BC cellline MDA-MB-231. In these cells it has been determined that RUNX1binds to its DNA motif at the end of RSPO3 first intron, which constitutesa relevant putative regulatory region of the human RSPO3gene, as indicated by combined bioinformatic studies of publiclyavailable data from chromatin immune-precipitation and assay fortransposase-accessible chromatin with sequencing (ChIP-seq andATAC-seq) as well as transcription factor (TF) binding motives inthe human genome. The goal of our present project is to analyzeRSPO3 expression in a set of human BC cell lines, which includesboth luminal (T47D and MCF-7) and basal (MDA-MB231 and BT-549) phenotypes, to determine relationships with information providedby publicly available data-sets about transcription modulatorsdifferentially recruited by the promoter and the intronic regulatoryregion in the human RSPO3 locus. Our results suggest that not onlyRUNX1, but also the estrogen receptor (ER), STAT3, co-repressorGroucho as well as the SWI/SNF chromatin remodeling complexmay exert relevant differential roles in regulating RSPO3 expressionin various breast cancer molecular subtypes.