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The United States Government as Represented by the Department of Veterans Affairs

Adhip P N Majumdar

Fazlul H Sarkar

This invention relates to ERRP (EGF-Receptor Related Protein) specific antibodies that could be used 1) to study the functional properties of ERRP and; 2) as a diagnostic and prognostic tool for malignancies. Preferably, the antibody reacts with a segment of ERRP containing 15 amino acids (SEQ ID NO: 4) that possesses the most antigenic property.

Antibodies to a novel EGF-receptor related protein (ERRP)

A cDNA fragment clone of 1583 base pairs with 90-95% sequence homology to the mouse EGFR and a truncated rat EGFR is described. The isolated cDNA is termed ERRP (EFG-Receptor Related Protein). In Northern-blot analysis with poly A&plus;RNA from different rat tissues, ERRP cDNA hybridized strongly to a mRNA transcript of about 1.8 kb. Maximal expression was noted in the small intestine, followed by colon, liver, gastric mucosa and other tissues. Transfection of ERRP cDNA in HCT-116 cells, a colon cancer cell line, markedly inhibits proliferation in monolayer and in soft agar and attenuates EGF-R tyrosine kinase activity. Transfection of ERRP in HCT-116 also delays tumor growth in SCID mice injected with these cells compared to the vector-transfector control cells. On the other hand, proliferation of the vector-transfected control, but not ERRP transfected HCT cells could be stimulated by TGF-&agr; (10 M and 10 M). The ERRP cDNA represents a new member of the EGFR gene family, and its protein product plays a key role in modulating the function of EGFR.

Recombinant DNA encoding an epidermal growth factor receptor related protein

A cDNA fragment clone of 1583 base pairs with 90-95% sequence homology to the mouse EGFR and a truncated rat EGFR is described. The isolated cDNA is termed ERRP (EFG-Receptor Related Protein). In Northern-blot analysis with poly A&plus; RNA from different rat tissues, ERRP cDNA hybridized strongly to a mRNA transcript of about 1.8 kb. Maximal expression was noted in the small intestine, followed by colon, liver, gastric mucosa and other tissues. Transfection of ERRP cDNA in HCT-116 cells, a colon cancer cell line, markedly inhibits proliferation in monolayer and in soft agar and attenuates EGF-R tyrosine kinase activity. Transfection of ERRP in HCT-116 also delays tumor growth in SCID mice injected with these cells compared to the vector-transfector control cells. On the other hand, proliferation of the vector-transfected control, but not ERRP transfected HCT cells could be stimulated by TGF-&agr; (10 M and 10 M). The ERRP cDNA represents a new member of the EGFR gene family, and its protein product plays a key role in modulating the function of EGFR.

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W. Bloomfield, MI, United States of America

Adhip P N Majumdar