Send to

Choose Destination
Oncogene. 1993 Nov;8(11):3047-53.

Hepatocyte growth factor transforms immortalized mouse liver epithelial cells.

Author information

Department of Pathology, Cancer Institute, Tokyo, Japan.


Transforming activity of hepatocyte growth factor (HGF) was demonstrated utilizing immortalized but not fully transformed mouse hepatocytes (MLE-10). Rat HGF cDNA, expressed under the control of a cytomegalovirus promoter, was transfected together with the neomycin resistance gene (PSV2neo) into MLE-10 cells by the calcium phosphate method, and propagated G418-resistant colonies were harvested colony by colony. After checking for integration and expression of exogenous HGF, five cell lines (MLE-10-HGF-1-5) were established. Three cell lines transfected with the vector only (MLE-10-CMV-1-3) were also established in the same manner. All MLE-10-HGF cell lines grew much faster than the MLE-10-CMV and original MLE-10 cells in culture and produced large colonies in soft agar, which colony production was blocked by the addition of anti-HGF antibody to the agar. After addition of HGF, original and MLE-10-CMV lines produced colonies in soft agar. The high-HGF-production lines (MLE-10-HGF-4 and -5) also gave rise to tumors within 2 weeks when implanted into the nude mice subcutis. In contrast, all MLE-10-CMV and original MLE-10 cells were negative in these growth assays. A rough parallelism between the level of HGF expression and the growth rate in both soft agar and nude mice subcutis was evident among MLE-10-HGF cell lines. Those with higher HGF production tended to grow in a scattered fashion in culture. High-affinity HGF receptor, HGFR/met, was expressed in MLE-10 and all the derived cell lines. Since HGF and/or HGFR/met gene expression is seen in various tumors and the serum HGF level is elevated in patients with hepatic disease, the present results indicate a possible significance of HGF and its receptor system in carcinogenesis, most probably via autocrine and/or paracrine mechanisms.

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center