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Glycine-Extended Gastrin Promotes the Growth of Lung Cancer

¹Gastroenterology Division and Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; ²Molecular Oncology, Roy Castle International Centre for Lung Cancer Research, The University of Liverpool, Liverpool, United Kingdom; ³Molecular Genetics and Oncology Group, Department of Clinical Dental Sciences, The University of Liverpool, Liverpool, United Kingdom; and ⁴The Physiological Laboratory, University of Liverpool, Liverpool, United Kingdom

The less processed forms of gastrin have recently been shown to act as trophic factors for both normal and malignant colonic cells. Although incompletely processed forms of gastrin such as glycine-extended gastrin and progastrin are also expressed in human lung cancers, the clinical significance of this expression has not been addressed. Consequently, we investigated the effects of overexpression of glycine-extended gastrin in a mouse strain that is prone to developing lung cancer and also examined the expression of incompletely processed gastrins in primary human lung cancers. We found that transgenic overexpression of glycine-extended gastrin in FVB/N mice resulted in a significant increase in the prevalence and growth of bronchoalveolar carcinoma. In addition, a substantial subset of human lung cancers was found to express progastrin and/or glycine-extended gastrin. Overexpression of glycine-extended gastrin by human lung cancers was associated with a significantly decreased survival. Taken together, these results suggest that glycine-extended gastrin may play a role in the growth and progression of some human lung cancers.

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