Collaborative interaction of Oct-2 with Oct-1 in transactivation of lactogenic hormones-induced β-casein gene expression in mammary epithelial cells

•Oct-2 mediates lactogenic hormones-induced β-casein gene expression.•Lactogenic hormones induce Oct-2 binding to the β-casein gene promoter.•Lactogenic hormones induce Oct-2 interactions with STAT5 and GR.•Oct-1 induces Oct-2 binding at the β-casein gene promoter.•Oct-2 forms a heteromer with Oct-1 regardless of hormone treatment.

Octamer-binding transcription factor-1 (Oct-1) is found to mediate lactogenic hormones (prolactin and glucocorticoids, HP)-induced β-casein gene expression in mammary alveolar secretory epithelial cells (MECs). The mammary gland also expresses Oct-2 isoform. In this study, we show that Oct-2 is also involved in HP-induced β-casein expression. Oct-2 endogenously binds to the β-casein promoter in MECs, and HP induce Oct-2 binding activity via mechanisms other than increasing Oct-2 expression or inducing Oct-2 translocation to the nucleus. Oct-2 transactivates HP-induced β-casein gene expression and this function is exchangeable with Oct-1. In MECs, Oct-2 is found to physically interact with Oct-1 regardless of HP treatment. However, HP induce physical interactions of Oct-2 with both signal transducer and activator of transcription 5 (STAT5) and glucocorticoid receptor (GR). These results provided biochemical evidence that Oct-2 may form a heteromer with Oct-1 in induction of β-casein gene expression by HP in MECs.