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(American Journal of Pathology. 1999;154:1323-1328.)
© 1999 American Society for Investigative Pathology

Short Communication

-Catenin-Deficient F9 Cells Differentiate into Signet Ring Cells

Yoshito Maeno^*, Seiji Moroi^*, Hirotaka Nagashima, Tetsuo Noda^§, Hitoshi Shiozaki, Morito Monden, Shoichiro Tsukita^* and Akira Nagafuchi^*

From the Department of Cell Biology,^*
Faculty of Medicine, Kyoto University, Kyoto, Japan; the Department of Surgery II,
Osaka University Medical School, Osaka, Japan; the Department of Cardiology,
Heart Institute of Japan, Tokyo Women's Medical College, Tokyo, Japan; and the Department of Cell Biology,^§
Cancer Institute, Tokyo, Japan

It has been demonstrated that -catenin is frequently lost in diffuse type adenocarcinomas. We have isolated -catenin-deficient mouse teratocarcinoma F9 cells by gene targeting. Wild-type F9 cell aggregates cultured in the presence of retinoic acid differentiated into embryoid bodies with an outer layer of epithelial cells. In contrast, cell aggregates of -catenin-deficient cells did not develop outer layers under the same conditions. The outer surface cells of -catenin-deficient cell aggregates, however, differentiated into epithelial cells as determined by their expression of epithelial marker proteins. These differentiated cells scattered from aggregates and showed signet ring cell morphology, which is frequently observed in diffuse type adenocarcinomas. We have provided clear evidence that a single mutation in the -catenin gene may be a direct cause not only of the scattered properties of cells but also of signet ring cell formation in diffuse type adenocarcinoma.

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