Altered phenotype of HT29 colonic adenocarcinoma cells following expression of the DCC gene.
On 18q, frequently deleted in late stage colorectal cancers, a gene, Deleted 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 tumors, which produce high levels of mucins, and seems to be preferentially expressed in intestinal goblet cells. To investigate whether DCC is related to mucin expression and can modulate the transformed phenotype, we introduced 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 DCC induce a mature goblet cell phenotype. However, HT29 clones expressing high and low levels of DCC protein showed a significant decrease in cell proliferation and tumorigenicity. Furthermore, increased shedding and an elevated rate of spontaneous apoptosis were associated with higher levels of expression of DCC. In summary, while restoration of DCC expression in a human colon carcinoma cell line did not influence expression of differentiation markers, DCC expression did affect the growth and tumorigenic properties of the cells suggesting that DCC can modulate the malignant phenotype of colon cancer.
Velcich
A
A
Department of Oncology, Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, New York 10467, USA.
Corner
G
G
Palumbo
L
L
Augenlicht
L
L
D000230:Adenocarcinoma / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000235:genetics*; D000075389:DCC Receptor; D016163:Genes, DCC; D020397:Goblet Cells / Q000166:cytology; D019073:HT29 Cells; D006801:Humans; D019656:Loss of Heterozygosity; D055262:Mucin-2; D009077:Mucins / Q000096:biosynthesis / Q000235:genetics; D010641:Phenotype; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000096:biosynthesis; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins