The PI's laboratory has recently discovered a novel, soluble truncated form of the receptor encoded by the proto-oncogene c-erbBI.(1-2) Preliminary data from the PI's laboratory and others suggest that the related proto-oncogenes, c-erbB2 and c-erbB3, also encode soluble receptor forms. (3-6) The c-erbB family of proto-oncogenes has been implicated in the development of both breast and ovarian carcinomas. In this application, we hypothesize that soluble forms of receptors encoded by the c-erbB family of proto-oncogenes may be important in ovarian carcinogenesis and mav have clinical utility as markers of disease activity, as prognostic indicators, and/or as potential targets for future therapeutic approaches. To test this hypothesis we propose to measure the serum levels of soluble forms of c-erbB receptors in a large cohort of women with advanced ovarian cancer. We will compare the expression of soluble receptors in serum with c-erbB expression in tumor cells as determined by immunohistochemical analysis. We will then compare c-erbB patterns of expression (in sera and tumor samples) with established histologic and clinical parameters. We also propose to delineate the molecular basis for the synthesis of soluble c-erbB receptor forms in ovarian tumors, and will test the ability of these soluble receptors to inhibit ovarian carcinoma cell growth in vitro.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA057534-02
Application #
3201880
Study Section
Pathology B Study Section (PTHB)
Project Start
1992-08-01
Project End
1997-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Baron, A T; Lafky, J M; Boardman, C H et al. (1999) Serum sErbB1 and epidermal growth factor levels as tumor biomarkers in women with stage III or IV epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 8:129-37
Baron, A T; Lafky, J M; Connolly, D C et al. (1998) A sandwich type acridinium-linked immunosorbent assay (ALISA) detects soluble ErbB1 (sErbB1) in normal human sera. J Immunol Methods 219:23-43
Lee, H; Maihle, N J (1998) Isolation and characterization of four alternate c-erbB3 transcripts expressed in ovarian carcinoma-derived cell lines and normal human tissues. Oncogene 16:3243-52
Baron, A T; Huntley, B K; Lafky, J M et al. (1997) Monoclonal antibodies specific for peptide epitopes of the epidermal growth factor receptor's extracellular domain. Hybridoma 16:259-71
Reiter, J L; Maihle, N J (1996) A 1.8 kb alternative transcript from the human epidermal growth factor receptor gene encodes a truncated form of the receptor. Nucleic Acids Res 24:4050-6
Hartmann, L C; Podratz, K C; Keeney, G L et al. (1994) Prognostic significance of p53 immunostaining in epithelial ovarian cancer. J Clin Oncol 12:64-9
Jenkins, R B; Bartelt Jr, D; Stalboerger, P et al. (1993) Cytogenetic studies of epithelial ovarian carcinoma. Cancer Genet Cytogenet 71:76-86