Mice carrying a truncated Apc gene have diminished gastric epithelial proliferation, gastric inflammation, and humoral immunity in response to Helicobacter felis infection.

Helicobacter pylori infection and adenomatous polyposis coli (Apc) gene mutations have been linked to gastric cancer in humans, but possible synergistic interaction(s) between these risk factors have not been examined. Fourteen C57BL/6 wild-type and 14 Apc1638 heterozygous mice were inoculated with Helicobacter felis at 6 weeks of age and compared at various time points with a similar number of uninfected control mice of the same genotype. Both infected and uninfected Apc1638 mice had a limited incidence of atypical proliferation foci in the mucosa of the antrum and pyloric junction at 4.5 and 6 months of age, whereas polyps of the antrum and pylorus were present in all mice, regardless of infection status, at 7.5 months. In contrast, no altered gastric mucosal foci were observed in control or infected C57BL/6 mice at any time point. Interestingly, the infected Apc1638 mice had less epithelial proliferation and inflammation in the body of the stomach, lower anti-H. felis serum IgG antibody responses (although both the wild-type and Apc mutant mice had a Th1-like immune response, based on a predominantly IgG2a immunoglobulin response), and higher bacteria and urease scores than did infected wild-type C57BL/6 mice. In conclusion, the Apc1638 truncating mutation leads to gastric dysplasia and polyposis of the antrum and pyloric junction, but H. felis infection of the Apc mutant mouse does not lead to an increased rate of gastric neoplasia. In addition, our data suggest this Apc mutation may actually lead to decreased immune, inflammatory, and gastric hyperplastic responses to Helicobacter infection, suggesting the possibility of a novel role for this tumor suppressor gene in the immune and local tissue responses to gastric bacterial infection.

Cytogenetic characterization of the human prostate cancer cell line P69SV40T and its novel tumorigenic sublines M2182 and M15.

Cytogenetic studies of a SV40T antigen immortalized human prostate epithelial cell line (P69SV40T) and its increasingly tumorigenic tumor sublines, designated M2182 and M15, were done with GTG-banding and multicolor fluorescence in situ hybridization (FISH). The parental line and each of the two sublines were near-diploid and contained several consistent abnormalities. Two structural chromosome anomalies were noted in all three lines; a der(7)t(5;20;7) and a der(5)t(5;9). Abnormalities that were acquired and retained in the tumor sublines after in vivo and/or in vitro selection included a der(1)t(1;8), der(3)t(3;14), der(20)t(7;20), and der(X)t(X;11). Findings unique to subline M2182 were a der(11)t(5;11) and -14. Those unique to M15 were a der(16)t(16;19) and -Y. Chromosome imbalances resulting from numerical and/or structural abnormalities in the tumor sublines involved several chromosome regions that have previously been implicated in human prostate cancer, such as loss of Xp, Y, 3p (M2182 and M15), 16q (M15), and gains for 5q (M2182) and 8q (M2182 and M15). Collectively, the characterization of these lines should assist with the localization of chromosome regions, and possibly genes, that are important in the development and progression of human prostate cancer.