Cells obtained from colorectal microadenomas mirror early premalignant growth patterns in vitro

Abstract

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 TGFα establishing an autocrine growth or survival pathway. However, in spite of autocrine TGFα 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 μmolar indicating that TGFα activated survival pathways in the early adenoma cell.