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Characterization of the Functional and Growth Properties of Cell Lines Established from Ileal and Rectal Carcinoid Tumors

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Abstract

Carcinoids of the intestine are the most common gastrointestinal carcinoid tumors. Therapeutic options to treat patients with these tumors are limited. There are very few ileal carcinoid cell lines available for in vitro studies to analyze new drugs that could be effective in treating patients with metastatic tumors. A replication defective recombinant adenovirus with an SV40 early T-antigen insert was used to infect two intestinal carcinoid tumors to create carcinoid cell lines. The cell lines were studied by cell culture, reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry. Both cell lines expressed SV40 large T antigen and receptors for TGFβ1, TGFβ2, EGFR, and somatostatin receptors. Treatment with TGFβ1 led to growth inhibition and increased apoptosis in the cultured cells. Octreotide inhibited cell growth of both cell lines while stimulating apoptosis. Treatment of the HC45 cells with gefitinib also inhibited cell growth in a concentration-dependent manner. TGFβ treatment stimulated chromogranin A expression while expression of two other granins, chromogranin B and 7B2, did not change significantly. RNA profiling of cells treated with TGFβ1 showed increased expression of vitamin D3 receptor. This finding was validated by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. These results indicate that these carcinoid cell lines can be used to study the proliferative and apoptotic mechanisms involved in intestinal carcinoid tumor growth regulation.

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Acknowledgments

This work was supported in part by a grant from Dr. and Mrs. Raymond R. and Beverly Sackler. The authors thank AstraZeneca, Great Britain for providing gefitinib and Dr. J.C. Thompson, University of Texas Medical Branch, Galveston, Texas for BON cell line.

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Authors and Affiliations

  1. Mayo Clinic College of Medicine, Rochester, MN, USA

    Gail A. Stilling, Heyu Zhang, Katharina H. Ruebel, Alexey A. Leontovich, Long Jin, Yoshinori Tanizaki, Shuya Zhang, Lori A. Erickson, Timothy Hobday & Ricardo V. Lloyd

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA

    Ricardo V. Lloyd

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  1. Gail A. Stilling
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  2. Heyu Zhang
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  3. Katharina H. Ruebel
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  4. Alexey A. Leontovich
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  5. Long Jin
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  6. Yoshinori Tanizaki
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  7. Shuya Zhang
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  8. Lori A. Erickson
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  9. Timothy Hobday
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  10. Ricardo V. Lloyd
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Correspondence to Ricardo V. Lloyd.

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Stilling, G.A., Zhang, H., Ruebel, K.H. et al. Characterization of the Functional and Growth Properties of Cell Lines Established from Ileal and Rectal Carcinoid Tumors. Endocr Pathol 18, 223–232 (2007). https://doi.org/10.1007/s12022-007-9001-3

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  • DOI: https://doi.org/10.1007/s12022-007-9001-3

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