Altered phenotype of HT29 colonic adenocarcinoma cells following expression of the DCC gene

On 18q, frequently deleted in late stage colorectal cancers, a gene, Delete d in Colon Cancer (DCC), has been identified and postulated to play a role as a tumor suppressor gene. DCC is retained in the majority of mucinous tum ors, which produce high levels of mucins, and seems to be preferentially ex pressed in intestinal goblet cells. To investigate whether DCC is related t o mucin expression and can modulate the transformed phenotype, we introduce d a full-length DCC cDNA into HT29 cells, which can be induced in vitro to express MUC2, the gene that encodes the major colonic mucin, Expression of DCC did not modulate constitutive or induced expression of MUC2, nor did DC C induce a mature goblet cell phenotype, However, HT29 clones expressing hi gh and low levels of DCC protein showed a significant decrease in cell prol iferation and tumorigenicity. Furthermore, increased shedding and an elevat ed rate of spontaneous apoptosis were associated with higher levels of expr ession of DCC, In summary, while restoration of DCC expression in a human c olon carcinoma cell line did not influence expression of differentiation ma rkers, DCC expression did affect the growth and tumorigenic properties of t he cells suggesting that DCC can modulate the malignant phenotype of colon cancer.