Context: HOX genes are highly evolutionarily conserved regulators of embryonic development. HOXA10 also regulates differentiation of the adult reproductive tract and mammary gland in response to sex steroids.

Objective: We recently identified two HOXA10 estrogen response elements. Here we demonstrate that estrogen responsive HOXA10 expression is cell type specific.

Design: In vitro study

Setting: Academic Medical center

Patients: N/A

Interventions: N/A

Main Outcome Measure: Reporter assay, gel shift assays (EMSA), immunohistochemistry

Results: The HOXA10 EREs and a Sp1 binding site differentially drive the cell type-specific E2 response. In EMSA both ER and bound both EREs but not the Sp1 site. In reporter assays both EREs and the Sp1 site demonstrated estrogen responsiveness and tissue specificity; transiently transfected uterine Ishikawa cells or breast MCF-7 cells showed differential responses to E2 treatment. Each response element (Sp1, ERE1 and ERE2) drove distinct differential expression in each cell type. Sp1 protein was expressed in a menstrual cycle stage specific expression pattern in endometrium, first expressed in peri-vascular cells.

Conclusions: Tissue specificity inherent to a regulatory element as well as differential cellular expression of transcription factors imparts differential tissue specific estrogen responsiveness.