title: Expression and functional coupling of liver β2 - adrenoceptors in the human hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. There are now multiple lines of evidence demonstrating that the β-adrenoceptor ( β-AR) signaling plays an important role in the progression and metastasis of cancer and may become a novel target for cancer therapy. Little information exists regarding the status of β-ARs and their postreceptor intracellular signaling cascade in the development of human HCC. This study was conducted to detect the expression signal transduction of the β-ARs in liver membranes obtained from patients with HCC and elucidate their possible implication on HCC development.
  
  
  METHODS
  The β-AR density and subtype distribution were determined by receptor binding studies. Protein levels of the β(2)-AR and G(s)(α) protein were determined by Western blot analysis. The receptor coupling efficiency and biochemical activities of the adenylate cyclase(AC) was also determined.
  
  
  RESULTS
  In HCC liver membranes, the β(2)-AR density was higher than the density in the nonadjacent nontumor liver membranes. The β(2)-AR protein expression was 1.5-fold increased as compared with nonmalignant controls, and positively correlated with the receptor density. The G s protein expression as well as the receptor, AC and G protein-stimulated activation of the cAMP formation was reduced in HCC.
  
  
  CONCLUSIONS
  The β(2)-AR was upregulated in human HCC. Despite this upregulation of the receptor,there was an altered postreceptor signal transduction in HCC liver. The mechanisms responsible for this change in the growth of HCC and the nature of this alteration remain unclear.
authors.affiliation: Department of Surgery II, Faculty of Medicine, University of Leipzig, Leipzig, Germany. Woubet.Kassahun@uniklinik-leipzig.de
authors.forename: Woubet T
authors.initials: WT
authors.lastname: Kassahun
authors.forename: Bianca
authors.initials: B
authors.lastname: Guenl
authors.forename: Fritz R
authors.initials: FR
authors.lastname: Ungemach
authors.forename: Sven
authors.initials: S
authors.lastname: Jonas
authors.forename: Getu
authors.initials: G
authors.lastname: Abraham
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020120:Iodocyanopindolol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551; D020120:Iodocyanopindolol; C049763:CGP 20712A; C033394:CGP 12177