ZAC1 target genes and pituitary tumorigenesis.

The zinc-finger protein Zac1 has a role as transcription factor and coregulator and plays an important role in pituitary development, maturation and tumorigenesis. Zac1 target genes control cell proliferation and hormone synthesis. While Zac1 is highly expressed in all hormone-producing cells of the pituitary, loss of expression frequently occurs in pituitary adenomas, in particular in non-functioning tumors. Zac1 lies downstream to the mitogenic MAPK and survival PI3K pathways. In turn, inhibition of the PI3K pathway by therapeutic agents, like somatostatin analogs up-regulate Zac1 expression. In fact Zac1 is an essential mediator of the antiproliferative effects of this treatment and correlates to successful outcome in acromegalic patients.