Ornithine Decarboxylase as a Biologic Marker in Familial Colonic Polyposis

Abstract

We investigated whether the activity of ornithine decarboxylase might serve as a diagnostic test for detecting the presence of the genotype for familial polyposis. This rate-limiting enzyme in the polyamine biosynthetic pathway is essential for intestinal mucosal proliferation. In colonic mucosa from 16 normal controls, ornithine decarboxylase activity was less than 2.5 nmol per milligram per hour. In contrast, it was higher than 2.5 nmol per milligram per hour in the normal-appearing areas of colonic mucosa from 11 of 13 patients with familial polyposis and in all polyps biopsied from these same subjects (P less than 0.05 for specimens from both sites, as compared with controls). Mucosa from dysplastic polyps showed higher mean ornithine decarboxylase activity than mucosa from polyps that were not dysplastic (P less than 0.05). In colonic mucosa from clinically unaffected, first-degree relatives of patients with familial polyposis, there was a bimodal distribution of ornithine decarboxylase activity, with one peak at the mean for normal controls and the other near the mean for normal-appearing mucosa from affected patients. Our study suggests that ornithine decarboxylase activity in colonic mucosa may reflect the abnormal proliferative state in familial polyposis and identify clinically normal family members who carry the genotype.

Colonic mucosal concentrations of folate correlate well with blood measurements of folate status in persons with colorectal polyps

“…Such a finding is not without precedent: widespread alterations in other biochemical and physiologic phenomena, such as ornithine decarboxylase activity (44)(45)(46) and crypt cell proliferation (47-51), were described previously in normal colorectal mucosa of persons prone to colorectal neoplasia. The anatomic extent of this aberration in colonic folate cannot be determined from this study because we sampled only the rectosigmoid junction; however, the fact that reduced folate concentrations were found distant from the adenomas implies that this is a widespread phenomenon that is not confined solely to the immediate vicinity of the adenoma.…”

Overexpression of antizyme-inhibitor in NIH3T3 fibroblasts provides growth advantage through neutralization of antizyme functions

“…The first and rate limiting enzyme in the polyamine biosynthesis pathway is ornithine decarboxylase (ODC, EC 4.1.1.17) . Ornithine decarboxylase activity is induced during growth stimulation of quiescent cells (Kahana and Nathans, 1984) and is constitutively increased in cells transformed by oncogenes (Holtta et al, 1988;Sistonen et al, 1989;Holtta et al, 1993), treated with carcinogens (Yuspa et al, 1976;Gilmour et al, 1985), infected by viruses (Don and Bachrach, 1975;Gazdar et al, 1976;Haddox et al, 1980), and in a variety of malignancies (Janne et al, 1983;Luk and Baylin, 1984;Pegg, 1988;Katz and Kahana, 1989;Tonin et al, 1989). Inhibition of ODC activity interferes with cellular transformation induced by proto-oncogenes (Auvinen et al, 1992;Holtta et al, 1993).…”

Cooperativity between the polyamine pathway and HER-2neu in transformation of human mammary epithelial cells in culture: Role of the MAPK pathway

“…ODC activity which is transiently increased upon growth factor exposure becomes constitutively activated during cell transformation (Gilmour et al, 1987). Elevated levels of ODC are frequently detected in transformed cell lines (Scalabrino and Ferioli, 1982), animal tumors (Scalabrino and Ferioli, 1981), and in some pre-neoplastic lesions (Luk and Baylin, 1984). In addition, induction of ODC activity and polyamine biosynthesis is critical in experimental animal models of carcinogenesis (O'Brien, 1976).…”