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12-O-Tetradecanoylphorbol-13-acetate Stimulation of DNA Synthesis in Cultured Preneoplastic Familial Polyposis Colonic Epithelial Cells but not in Normal Colonic Epithelial Cells¹

Laboratory of Gastrointestinal Cancer Research [E. F., M. L.] and the Department of Medicine [S. G., M. L.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021

We have developed a method for the routine primary culture of human colonic epithelial cells. Cultured cells exhibited characteristic epithelial structures, including a brush border and junctional complexes. Flask-like goblet cells containing mucus were also seen within the epithelial monolayer. [³H]Thymidine labeling indices were used to distinguish between cultured cells from familial polyposis patients, other patients at high risk to develop colon cancer, and low-risk control subjects. 12-O-Tetradecanoylphorbol-13-acetate (TPA) at 10 ng/ml enhanced DNA synthesis an average of 8-fold when assayed by labeling index in colonic epithelial cells from five of six familial polyposis patients. No such stimulation by TPA was seen in cells from 13 high-risk patients without familial polyposis or in cells from five low-risk subjects. Hundreds of benign polyps can be found in the colons of familial polyposis patients. One such benign tubular adenoma exhibited the same enhancement of DNA synthesis by TPA as normal-appearing epithelial cells from a biopsy adjacent to that polyp. Mitogenic response to TPA had been seen earlier in cells from each of four tubular adenomas (Friedman, E. Cancer Res., 41: 4588–4599, 1981). Both familial polyposis epithelial cells and adenoma cells are considered preneoplastic, but they are not identical because their patterns of actin cytoskeletal organization differ. These results imply that familial polyposis epithelial cells are precursors of tubular adenoma cells, and their transition to the more advanced preneoplastic cells of this benign tumor is influenced by endogeneous tumor promoters.

¹ This investigation was supported by USPHS Grants 28822 from the National Large Bowel Cancer Project and 08748 awarded by the National Cancer Institute, Department of Health and Human Services, and Grant SIG-7 from the American Cancer Society.

² To whom requests for reprints should be addressed, at the Laboratory of Gastrointestinal Cancer Research, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 1/25/84. Accepted 6/ 4/84.

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