Autocrine motility factor-receptor in human bladder-carcinoma - gene-expression, loss of cell-contact regulation and...

Cell lines derived from normal (FHs738BL), papilloma (RT4) and carcinoma (J82) human urinary bladder tissue were characterized for motility and for expression of autocrine motility factor (AMF) receptor, i.e. the 78 kDa cell surface glycoprotein, gp78. Further, the human gene for gp78 was mapped to the long arm of chromosome 16, band q21 just distal to 16q13. Although the papilloma cells were immotile, the normal and carcinoma cells exhibited similar basal migration, while only the carcinoma cells were capable of responding to tumor-derived AMF. No difference in gene structure or copy number was found among the three cell lines and all expressed gp78. Cell surface distribution and level of expression distinguished the three cell populations with a markedly concentrated display of gp78 in focal regions on the surface of the carcinoma cells. Cell contact down-regulated gp78 expression in the normal but not the carcinoma cells. In this model for bladder carcinoma, malignancy is apparently associated in part with the spatial localization of gp78 on the cell surface, coupled with a loss of contact inhibition-mediated gp78 downregulation, the result of which is an AMF-receptive signal transduction motility response.