Correlation of Pit-1 gene expression and Pit-1 content with proliferation and differentiation in human myeloid leukemic cells.

ABSTRACT

The transcription factor pituitary-1 (Pit-1) is a homeodomain-containing protein that is expressed mainly in the pituitary, where it drives the expression of growth hormone, prolactin, and thyroid-stimulating hormone beta chain genes. In addition, Pit-1 is required for adequate pituitary cell growth and may be involved in the pathogenesis of pituitary adenomas. Pit-1 expression has been also reported in nonpituitary tissues, where it might be involved in the control of cell proliferation. In order to elucidate such a possibility, we have investigated the changes in both Pit-1 mRNA and Pit-1 immunoreactivity in HL-60 cells following the addition of several differentiating agents. Our results show that while high Pit-1 levels are found in exponentially growing HL-60 cells, a significant decrease occurs after induction of cells to differentiate along the macrophage lineage with 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast no changes were observed when cells were treated with interferon-alpha, which also induces differentiation of HL-60 cells that, at odds with TPA, is not accompanied with growth arrest. In all, these findings suggest that Pit-1 expression is specifically associated with proliferation in HL-60 cells, thus supporting the idea that one of the functions of nonpituitary Pit-1 may be the control of cell proliferation.