ENDOGENOUS HUMAN RENIN EXPRESSION AND PROMOTER ACTIVITY IN CALU-6, A PULMONARY-CARCINOMA CELL-LINE

We have previously reported that transgenic mice containing the human renin gene express high levels of human renin mRNA in the lung. We sho w in this report that human renin expression in two lines of transgeni c mice is developmentally regulated. Human renin expression is not evi dent in the transgenic mouse lung at 15.5 days of gestation, is detect able at 17.5 days of gestation, peaks around birth, and remains elevat ed into adulthood. In situ hybridization of mouse fetal lung samples a t 18.5 days of gestation revealed that human renin was exclusively exp ressed in pulmonary type II epithelial cells. A survey of the medical literature revealed a number of clinical cases in which hypertension w as caused by renin-secreting pulmonary tumors and a fairly widespread occurrence of immunoreactive renin in banked pulmonary tumors of diver se origin. This prompted us to examine a number of pulmonary tumor cel l lines to determine whether they express human renin mRNA. One pulmon ary carcinoma cell line, CALU-6, expressed human renin mRNA endogenous ly. Human renin expression in these cells was induced approximately 10 0-fold after treatment with forskolin, 8-bromoadenosine 3':5'-cyclic m onophosphate, or N-6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphat e. Transfection analysis of human renin promoter-luciferase fusion con structs revealed the presence of cell-specific positive and negative r egulatory elements in the human renin 5'-flanking DNA. This cell line is the only immortalized human cell line that expresses high levels of endogenous human renin mRNA and should provide an excellent tool for studying the regulation of human renin expression in vitro.