Aim: 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.
Conclusion: 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.