SUPPRESSION OF ENDOMETRIAL CARCINOMA CELL TUMORIGENICITY BY HUMAN-CHROMOSOME-18

Presumptive tumor suppressor genes may be localized to specific chromo somes by the procedure of microcell fusion, whereby individual chromos omes derived from normal human cells are introduced into tumor cells. Allelic loss on chromosome 18 is commonly seen in endometrial carcinom a, and the DCC gene on chromosome arm 18q is a potential human tumor s uppressor gene. In this study, we investigated the hypothesis that a g ene on chromosome 18, possibly DCC, is capable of suppressing the tumo rigenicity of endometrial carcinoma cells. Microcells from the mouse A 9 cell clone containing one human chromosome 18 tagged with the pSV2-n eo plasmid were fused with the highly tumorigenic endometrial carcinom a cell lines HHUA and Ishikawa, and G418-resistant microcell hybrids c ontaining an extra copy of chromosome 18 were isolated. Clones isolate d from the HHUA cell line were completely suppressed for tumorigenicit y in nude mice, and clones from the Ishikawa line were suppressed or i nhibited for tumorigenicity. In contrast, growth rates in vitro were n ot significantly affected in clones from either parental cell line. DC C expression was elevated in most of the suppressed hybrids. These res ults indicate that a gene on human chromosome 18 is capable of suppres sing the tumorigenicity of endometrial carcinoma cells, and that DCC i s a candidate for this endometrial carcinoma tumor suppressor gene. (C ) 1995 Wiley-Liss, Inc.