Growth of mouse hepatocytes is stimulated by gastrin

✍ Scribed by Chong Zheng Yao; Richard J. Bold; Jin Ishizuka; Courtney M. Townsend Jr.; James C. Thompson

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 682 KB
• Volume: 163
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041630313

✦ Synopsis

Hepatocyte growth is regulated by various growth factors, including epidermal growth factor (EGF) and insulin. Recently, several additional peptide hormones have been shown to stimulate growth of hepatocyte only in the presence of EGF or insulin and are thus termed secondary mitogens. Gastrin regulates growth of normal and neoplastic gastrointestinal tissues, but the effect on growth of hepatocyte is unknown. We examined the effect of gastrin on growth of a normal mouse hepatocyte (NMH) line established in our laboratory. Effect of gastrin-1 7 (G-17) (lo-" to lO-'M) on growth of N M H cells was examined in either the presence or absence of EGF in the culture medium. Growth of N M H cells was evaluated by incorporation of either bromodeoxyuridine (BrdU) or 3H-thymidine and by counting cells. Presence of a cell-surface receptor for G-17 was determined by Scatchard analysis using 1251-G-l 7. In the presence of EGF, gastrin stimulated growth of N M H cells; in the absence of EGF, gastrin did not affect growth. The stimulatory effect of gastrin on N M H cells was blocked by JMV 320, a CCK-B type receptor antagonist. N M H cells possess a single, high affinity binding site for gastrin (Kd = 1.2 nM); EGF increased the gastrin binding capacity compared to nontreated cells (3.5 * 0.4 vs. 2.2 ? 0.6 fmol/106 cells). G-17 stimulated growth of N M H cells through a single high affinity receptor for G-17 which pharmcologically appears to be the CCK-B type only in the presence of EGF and thus can be considered a secondary mitogen.