Cells obtained from colorectal microadenomas mirror early premalignant growth patterns in vitro.
LT97, a permanent cell line consisting of epithelial cells with an early premalignant genotype was established from small colorectal polyps. LT97 cells have lost both alleles of the APC tumour suppressor gene. In addition, they carry a mutated Ki-ras oncogene, while TP53 is normal. LT97 growth characteristics are thus representative of early adenomas. They had to be passaged as multicellular aggregates indicating a dependency of survival on cell-cell contact and in accordance with their premalignant genotype were not capable of growth in soft agar. LT97 cells did express both the EGF-receptor and small amounts of TGF(alpha) establishing an autocrine growth or survival pathway. However, in spite of autocrine TGF(alpha) production, growth was strongly dependent on exogenous growth factors--mainly EGF, insulin and HGF. Inhibition of the EGF-receptor kinase induced apoptosis at an IC(50) concentration of 4 micromolar indicating that TGF(alpha) activated survival pathways in the early adenoma cell.
Richter
M
M
Institute of Cancer Research, University of Vienna, Borschkegasse 8a, A 1090 Vienna, Austria.
Jurek
D
D
Wrba
F
F
Kaserer
K
K
Wurzer
G
G
Karner-Hanusch
J
J
Marian
B
B
D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D017209:Apoptosis; D002455:Cell Division; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D005434:Flow Cytometry; D011905:Genes, ras; D006801:Humans; D009154:Mutation / Q000235:genetics; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016211:Transforming Growth Factor alpha