Human growth hormone gene expression in rat but not human non-pituitary cells after stable gene transfer

Tissue-specific expression of the rat growth hormone (rGH) gene requires binding of a pituitary-specific factor. Binding of this factor has been used to explain tissue-specific expression of the human growth hormone (hGH-N) gene in transfected rat pituitary (GC) tumour cells. Neither rat fibroblast (R2) nor human cervical carcinoma (HeLa) cells contain the rat pituitary-specific factor. Thus, no expression of hGH-N or rGH would be expected in these cells. R2 cell lines containing stably integrated hGH-N or rGH genes were generated. Expression of hGH-N but not rGH was detected. By contrast, stably transfected HeLa cells did not express the endogenous or transfected hGH-N genes. However, an hGH-N transcript was detected when hGH-N gene expression was directed by a viral promoter. This suggests that the block in expression occurs at the level of transcription and not mRNA stability. Hybrid genes containing 496 base pairs (bp) of hGH-N or 234 bp of rGH 5'-flanking DNA, including promoter sequences, fused to the bacterial gene coding for chloramphenicol acetyltransferase were used to stably transfect R2 cells. The hybrid hGH-N gene was more active than a promoterless construction in these cells. By contrast, the hybrid rGH gene was not. These data suggest that the hGH-N gene can be activated by rat transcription factors other than those found in pituitary cells.