Hormonal regulation of expression of the angiotensinogen gene in cultured mouse hepatoma cells.
To investigate the hormonal regulation of expression of the angiotensinogen (ANG) gene in the liver, we constructed fusion genes with various lengths of the 5'-flanking region of the rat ANG gene linked to a bacterial chloramphenicol acetyl transferase (CAT) gene as reporter and introduced them into mouse hepatoma cells (Hepa 1-6). As a negative control, we introduced them into a nonhepatic cell line, a mouse testicular Sertoli (TM4) cell line. The level of expression of ANG-CAT fusion genes, pOCAT (ANG N-1498/+18), pOCAT (ANG N-688/+18), pOCAT (ANG N-110/+18), pOCAT (ANG N-53/+18) and (ANG-35/+18) were 3.7, 4, 1.1, 4, and 3-fold higher than promoterless pOCAT in Hepa 1-6 cells. No significant expression of any of these ANG-CAT fusion genes over the promoterless pOCAT was observed in Sertoli TM4 cells. The addition of dexamethasone (10(-10) to 10(-4) mol/L) stimulated the expression of the pOCAT (ANG N-1498/+18) fusion gene in Hepa 1-6 cells in a dose-dependent manner with a maximum stimulation at 10(-4) mol/L and a half-maximal stimulation at 10(-8) mol/L. A combination of dexamethasone (10(-6) mol/L) and 8-bromo-cyclic AMP (cAMP) (10(-3) mol/L) further enhanced the effect of the dexamethasone alone although cAMP alone had no effect. Testosterone (10(-6) mol/L), estradiol (10(-6) mol/L), progesterone (10(-6) mol/L), and thyroid hormone (L-T3, 10(-6) mol/L) did not have this effect in either the presence or absence of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
University of Montréal, Maisonneuve-Rosemont Hospital, Québec, Canada.
M
M
Ming
R
R
Sikstrom
S
S
Lachance
A
A
Delalandre
S
S
Carrière
J S
JS
Chan
D000199:Actins / Q000032:analysis / Q000235:genetics; D000808:Angiotensinogen / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000199:Actins; D012333:RNA, Messenger; D014284:Triiodothyronine; D000808:Angiotensinogen; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase