Gastrin gene expression is required for the proliferation and tumorigenicity of human colon cancer cells

Pomila Singh, Azar Owlia, Andrea Varro, Bosong Dai, S. Rajaraman, Thomas Wood

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The majority of human colon cancers express the gastrin gene, and a significant percentage bind gastrin-like peptides. However, it is not known if gastrin gene products are physiologically relevant to the growth and proliferation of human colon cancers. To investigate the functional role of gastrin gene expression, we examined the effect of gastrin antisense (AS) RNA expression on the growth and tumorigenicity of colon cancer cells. The full- length human gastrin cDNA was cloned in the AS direction in a retroviral vector under the transcriptional control of human cytomegalovirus promoter. Three representative human colon cancer cell lines that expressed negligible (Colo-205A) to significant (Colo-320 and HCT-116) levels of gastrin mRNA were transfected with either AS or control vectors and subjected to various growth studies in vitro and in vivo. The proliferative and tumorigenic potential of the AS clones from the gastrinexpressing cell lines was significantly suppressed compared to that of the control clones, whereas the growth of Colo-205A-AS cells (the negative control) was similar to that of the Colo- 205A-C-cells, indicating the relative specificity of the antitumorigenic effects of AS gastrin RNA expression. We believe that this is the first evidence that supports a possible critical role of gastrin gene expression in the tumorigenicity of human colon cancers that express the gastrin gene. Because >60-80% of human colon cancers express the gastrin gene, it can be expected that the growth of a significant percentage of these cancers may be critically dependent on the expression of gastrin gene products. Therapeutic measures, such as the AS strategy used in the present study, may therefore prove to be useful in treating human colon cancers in the future.

Original languageEnglish (US)
Pages (from-to)4111-4115
Number of pages5
JournalCancer Research
Volume56
Issue number18
StatePublished - Sep 15 1996

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Gastrins
Colonic Neoplasms
Gene Expression
Growth
Antisense RNA
Genes
Clone Cells
Cell Line
Cytomegalovirus
Complementary DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Singh, P., Owlia, A., Varro, A., Dai, B., Rajaraman, S., & Wood, T. (1996). Gastrin gene expression is required for the proliferation and tumorigenicity of human colon cancer cells. Cancer Research, 56(18), 4111-4115.

Gastrin gene expression is required for the proliferation and tumorigenicity of human colon cancer cells. / Singh, Pomila; Owlia, Azar; Varro, Andrea; Dai, Bosong; Rajaraman, S.; Wood, Thomas.

In: Cancer Research, Vol. 56, No. 18, 15.09.1996, p. 4111-4115.

Research output: Contribution to journalArticle

Singh, P, Owlia, A, Varro, A, Dai, B, Rajaraman, S & Wood, T 1996, 'Gastrin gene expression is required for the proliferation and tumorigenicity of human colon cancer cells', Cancer Research, vol. 56, no. 18, pp. 4111-4115.
Singh, Pomila ; Owlia, Azar ; Varro, Andrea ; Dai, Bosong ; Rajaraman, S. ; Wood, Thomas. / Gastrin gene expression is required for the proliferation and tumorigenicity of human colon cancer cells. In: Cancer Research. 1996 ; Vol. 56, No. 18. pp. 4111-4115.
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