Esophageal cancers have a unique geographical distribution yet contribute to cancer mortality worldwide. There is an important relationship between genetic factors and the development of cancers. While loss of heterozygosity (LOH), mutations, deletions, and amplifications of genes are reported for esophageal cancers, functional evidence for the involvement of chromosomal regions in this cancer is still lacking....[ Read more ]

Esophageal cancers have a unique geographical distribution yet contribute to cancer mortality worldwide. There is an important relationship between genetic factors and the development of cancers. While loss of heterozygosity (LOH), mutations, deletions, and amplifications of genes are reported for esophageal cancers, functional evidence for the involvement of chromosomal regions in this cancer is still lacking.

Microcell-mediated chromosome transfer (MMCT) is a powerful functional approach to study the involvement of tumor suppressor genes (TSGs) in cancers. The introduction of a normal copy of certain chromosomes has been observed to have tumor suppressive effects on various cancer cell lines. In this project, MMCT was employed to investigate the effects of the introduction of normal intact copies of chromosomes 3 and 17 into the esophageal carcinoma cell line T.Tn.

Tumorigenicity assays for hybrid clones obtained from transferring intact and different deletion fragments of the two chromosomes showed variable results. After thorough investigation, the parental recipient cell line T.Tn was found to contain a mixed population of highly tumorigenic cells and non-tumorigenic cells. Hence the observed suppression of tumor growth in vivo of the hybrid clones may have been caused by this heterogeneity. Only results from the few tumorigenic clones were clearly reliable. Microsatellite analysis of the recipient and donor cell lines, and the hybrids and their tumor segregants showed a frequent loss of regions of donor chromosomes in the hybrid clones with a strong selection pressure for clones able to expand in vitro. Two regions on each of those two chromosomes (3p24.2-22 and 3q27 on chromosome 3; 17p13.1 and 17q11.2-12 on chromosome 17) may play an important role in cell growth properties in vitro and/or in vivo.