12-O-TETRADECANOYLPHORBOL-13-ACETATE STIMULATION OF DNA-SYNTHESIS IN CULTURED PRENEOPLASTIC FAMILIAL POLYPOSIS COLONIC EPITHELIAL-CELLS BUT NOT IN NORMAL COLONIC EPITHELIAL-CELLS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (9) , 4078-4086
Abstract
A method for the routine primary culture of human colonic epithelial cells was studied. Cultured cells [from humans] 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 5 of 6 familial polyposis patients. No such stimulation by TPA was seen in cells from 13 high-risk patients without familial polyposis or in cells from 5 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 was seen earlier in cells from each of 4 tubular adenomas. Both familial polyposis epithelial cells and adenoma cells are considered preneoplastic, but they are not identical because their patterns of actin cytoskeletal organization differ. Familial polyposis epithelial cells evidently are precursors of tubular adenoma cells; their transition to the more advanced preneoplastic cells of this benign tumor is influenced by endogenous tumor promoters.