Tumor development by transgenic expression of a constitutively active insulin-like growth factor I receptor.

Abstract

The insulin-like growth factor I receptor (IGF-IR) is a transmembrane tyrosine kinase that is essential to growth and development and also thought to provide a survival signal for the maintenance of the transformed phenotype. There has been increasing interest in further understanding the role of IGF-I signaling in cancer and in developing receptor antagonists for therapeutic application. We describe herein a novel animal model that involves transgenic expression of a fusion receptor that is constitutively activated by homodimerization. Transgenic mice that expressed the activated receptor showed aberrant development of the mammary glands and developed salivary and mammary adenocarcinomas as early as 8 weeks of age. Xenograft tumors and a cell line were derived from the transgenic animals and are sensitive to inhibition by a novel small-molecule inhibitor of the IGF-IR kinase. This new model should provide new opportunities for further understanding how aberrant IGF-IR signaling leads to tumorigenesis and for optimizing novel antagonists of the receptor kinase.

• Authors: Joan M Carboni, Adrian V Lee, Darryl L Hadsell, Bruce R Rowley, Francis Y Lee, David K Bol, Amy E Camuso, Marco Gottardis, Ann F Greer, Ching Ping Ho, Warren Hurlburt, Aixin Li, Mark Saulnier, Upender Velaparthi, Cindy Wang, Mei-Li Wen, Richard A Westhouse, Mark Wittman, Kurt Zimmermann, Brent A Rupnow, Tai W Wong
• Journal: Cancer research (Cancer Res) Vol. 65 Issue 9 Pg. 3781-7 (May 01 2005) ISSN: 0008-5472 [Print] United States
• PMID: 15867374 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CD8 Antigens
• Recombinant Fusion Proteins
• Receptor, IGF Type 1

Topics

• Adenocarcinoma (genetics, metabolism, pathology)
• Animals
• CD8 Antigens (biosynthesis, genetics)
• Cell Transformation, Neoplastic (genetics, metabolism, pathology)
• Female
• Humans
• Mammary Neoplasms, Experimental (enzymology, genetics, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Mice, Nude
• Mice, Transgenic
• Neoplasm Transplantation
• Pregnancy
• Receptor, IGF Type 1 (antagonists & inhibitors, biosynthesis, genetics)
• Recombinant Fusion Proteins (biosynthesis, genetics)
• Salivary Gland Neoplasms (enzymology, genetics, pathology)
• Transfection
• Transgenes (genetics)
• Transplantation, Heterologous