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

Oncogene volume 18, pages 2599–2606 (1999)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr B Vogelstein for the generous gift of the CMV – DCC expression plasmid, and critical reading of the manuscript. This work was supported by Grants CA-55913, CA-68965 and P30-13330 from the National Cancer Institute.

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  1. Departments of Surgery and Pathology, Children's Hospital and Harvard Medical School, Boston, 02115, MA, USA

    Anna Velcich, Georgia Corner, Lisa Palumbo & Leonard Augenlicht

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  1. Anna Velcich
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  4. Leonard Augenlicht
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Velcich, A., Corner, G., Palumbo, L. et al. Altered phenotype of HT29 colonic adenocarcinoma cells following expression of the DCC gene. Oncogene 18, 2599–2606 (1999). https://doi.org/10.1038/sj.onc.1202610

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