Suppression of endometrial carcinoma cell tumorigenicity by human chromosome 18.
Presumptive tumor suppressor genes may be localized to specific chromosomes by the procedure of microcell fusion, whereby individual chromosomes derived from normal human cells are introduced into tumor cells. Allelic loss on chromosome 18 is commonly seen in endometrial carcinoma, and the DCC gene on chromosome 18q is a potential human tumor suppressor gene. In this study, we investigated the hypothesis that a gene on chromosome 18, possibly DCC, is capable of suppressing the tumorigenicity of endometrial carcinoma cells. Microcells from the mouse A9 cell clone containing one human chromosome 18 tagged with the pSV2-neo plasmid were fused with the highly tumorigenic endometrial carcinoma cell lines HHUA and Ishikawa, and G418-resistant microcell hybrids containing and extra copy of chromosome 18 were isolated. Clones isolated from the HHUA cell line were completely suppressed for tumorigenicity in nude mice, and clones from the Ishikawa line were suppressed or inhibited for tumorigenicity. In contrast, growth rates in vitro were not significantly affected in clones from either parental cell line. DCC expression was elevated in most of the suppressed hybrids. These results indicate that a gene on human chromosome 18 is capable of suppressing the tumorigenicity of endometrial carcinoma cells, and that DCC is a candidate for this endometrial carcinoma tumor suppressor gene.
Yamada
H
H
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Sasaki
M
M
Honda
T
T
Wake
N
N
Boyd
J
J
Oshimura
M
M
Barrett
J C
JC
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002459:Cell Fusion; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002871:Chromosome Banding; D002887:Chromosomes, Human, Pair 18; D000075389:DCC Receptor; D004247:DNA / Q000032:analysis; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016163:Genes, DCC / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C501910:Dcc protein, mouse; D005819:Genetic Markers; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D004247:DNA