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The Helix-Loop-Helix Protein Id2 Is Overexpressed in Human Pancreatic Cancer¹

Departments of Medicine, Biological Chemistry, and Pharmacology, University of California, Irvine, California 92697 [J. K., T. I., M. K.]; Department of Visceral and Transplantation Surgery, University of Bern, 3010 Bern, Switzerland [H. F., M. W. B.]; and Preuss Laboratory, Department of Neurological Surgery, University of California, San Francisco, California 94143 [M. A. I.]

Id2 belongs to the Id family of helix-loop-helix (HLH) proteins, which upon heterodimerization with basic HLH proteins prevent basic HLH proteins from DNA binding. Proteins of the Id family act as negative regulatory transcriptional factors, and their expression correlates with cell proliferation and arrested differentiation in many cell lineages. In this study, we characterized the expression of Id2 in normal and cancerous pancreatic tissues. Pancreatic cancers markedly overexpressed Id2 mRNA in comparison to the normal pancreas. Furthermore, there was abundant Id2 immunoreactivity in the cancer cells within the pancreatic tumor mass. In PANC-1 human pancreatic cancer cells, steady-state Id2 mRNA levels increased upon serum addition and decreased after induction of differentiation with either sodium butyrate or 12-O-tetradecanoylphorbol-13-acetate. Inhibition of Id2 expression with Id2 antisense oligonucleotides inhibited the growth of these cells, whereas random and sense oligonucleotides were without effect. These findings suggest that Id2 may have a role in human pancreatic cancer.

¹ This work was supported by USPHS Grants CA-40162 (to M. K.). J. K. was the recipient of a fellowship award from the University of California Research and Education Grant on Gene Therapy for Cancer.

² To whom requests for reprints should be addressed, at Division of Endocrinology, Diabetes and Metabolism, Medical Sciences I, C240, University of California, Irvine, CA 92697. Phone: (714) 824-6887; Fax: (714) 824-1035.

Received 6/19/98. Accepted 7/17/98.

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