P4HTM: A Novel Downstream Target of GATA3 in Breast Cancer

Abstract

Abstract Breast cancer continues to be a major cause of death among women. The GATA3 gene is often overexpressed in breast cancer and is widely used to support a diagnosis. However, lower expression of GATA3 has been linked to poorer prognosis along with frequent gene mutations. Therefore, the role of GATA3 in breast cancer appears to be context specific. This study aims to identify a new downstream target of GATA3 to better understand its regulatory network. Clinical data analysis identified the prolyl 4-hydroxylase transmembrane protein (P4HTM) as one of the most highly co-expressed genes with GATA3. Immunohistochemical staining of breast tumors confirms co-expression between GATA3 and P4HTM at the protein level. Similar to GATA3, P4HTM expression levels are linked to patient prognosis, with lower levels indicating poorer survival. Genomics data found that GATA3 binds to the P4HTM locus, and that ectopic expression of GATA3 in basal breast cancer cells increases the P4HTM transcript level. These results collectively suggest that P4HTM is a novel downstream target of GATA3 in breast cancer and is involved in tumor progression.