Immortalization of a human colorectal adenoma cell line by continuous in vitro passage: possible involvement of chromosome 1 in tumour progression.

A non-tumorigenic epithelial cell line designated PC/AA, derived from a large pre-malignant colorectal adenoma from a patient with familial polyposis coli (also referred to as hereditary adenomatosis of the colon and rectum) has become immortal in vitro. PC/AA has been passaged in vitro continuously for over 4 years and shows no signs of senescence. At early passage, PC/AA has a normal diploid karyotype but with late passage is showing signs of progression, becoming aneuploid and displaying signs of morphological transformation. Every cell examined of late-passage PC/AA has an isochromosome (1q), and one other marker chromosome which is probably derived from an additional chromosome 8. The majority of cells examined have 48 chromosomes. Despite showing signs of progression in vitro, late-passage PC/AA has remained non-tumorigenic in athymic nude mice and retained morphological differentiation characteristics of colonic cells, in particular the ability to synthesize and secrete mucin. Two other cell lines derived from small adenomas did not become immortal in vitro and were also non-tumorigenic in athymic nude mice. The isolation of an immortal pre-malignant human epithelial cell line could prove invaluable in studies on human carcinogenesis and tumour progression. Our results, showing that only a large adenoma and no small adenomas have given rise to immortal cell lines, raise the possibility that the acquisition of in vitro immortality is associated with a relatively late stage in the adenoma-carcinoma sequence. The possible involvement of chromosome 1 in tumour progression is discussed.