The epidermal growth factor receptor is a 170,000 dalton glycoprotein composed of three domains. The cell surface domain binds epidermal growth factor (EGF) and a low molecular weight tumor specific growth factor (TGF Alpha). Autocrine stimulation of the EGF receptor occurs when the same tumor cell possesses EGF receptors and also produces TGF Alpha. The receptor has a hydrophobic membrane spanning domain connecting the cell surface region with the intracellular tyrosine specific protein kinase domain. The EGF receptor shares regions of primary sequence homology with the src family of protein kinases and most closely resembles the v-erb-B and recently discovered neu gene. EGF receptor amplification has been demonstrated in the A431 carcinoma cell line raising the possibility that elevated or aberrant EGF receptor expression may represent a diagnostically useful feature of certain classes of human cancers. In Phase I of this project, methods will be developed for preparative isolation of human EGF receptor from A431 cells using ricin B chain, ion exchange, and EGF affinity chromatography. The protein kinase C phosphorylation substrate sequence flanking threonine 654 will be produced by solid-phase peptide synthesis. Mice will be immunized, hyperimmune sera produced and hybridoma fusions will be initiated. Phase II experiments will be designed to develop panels of monoclonal antibodies to both native and formalin fixed EGF receptors. These will be analyzed for potential use in histopathology, in vivo imaging and a serum based antigen capture test for receptor protein.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA040866-01A1
Application #
3491157
Study Section
(SSS)
Project Start
1986-09-30
Project End
1987-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Osi Pharmaceuticals, Inc.
Department
Type
DUNS #
City
Uniondale
State
NY
Country
United States
Zip Code
11553