The transactivation-competent carboxyl-terminal domain of AF-9 is expressed within a sexually dimorphic transcript in...

We have investigated the biological role of the cellular counterpart of the leukemogenic AF-9 gene by cloning the rat AF-9 (rAF-9) cDNA and defining the regulation of an anterior pituitary-specific rAF-9 transcript that is expressed in a sexually dimorphic manner. Expression of this transcript is down-regulated after puberty in females and can be subsequently up-regulated in adults by ovariectomy. Hormone replacement studies have provided direct evidence that rAF-9 mRNA expression is suppressed by estrogen. Mapping the 1.9 kb anterior pituitary transcript has shown that it corresponds in size to the rAF-9 cDNA clone, which contains an open reading frame (ORF) that is truncated compared with the human AF-9 ORF, but encodes a previously defined transcriptional activation domain. Thus, the cellular AF-9 gene is alternatively expressed in a manner that reflects the presence of translocated, functionally active (oncogenic) AF-9 sequences in leukemias. Using a novel antisera raised against a rAF-9 peptide, we have also demonstrated tissue- and sex-specific expression of a nuclear 41 kDa anterior pituitary protein and have localized this protein to a major population of growth hormone synthesizing cells. By localizing the expression and defining the physiological regulation of rAF-9, our studies have provided novel insights into the AF-9 gene that will facilitate an understanding of both oncogenic and endocrine roles.