Abstract

CA125 is expressed on the surface of ovarian carcinoma cells. It is either sloughed or secreted so that significant levels are detected in serum. Serum levels of CA125 correlate with progression or regression of clinical disease and thereby provide a monitoring system for the therapeutic management of these patients. Neither the functional relationship of CA125 to malignancy (if any) or the structure of CA125 have been established. It has been established that CA125 is part of a mucin-like carbohydrate complex and that CA125 is intimately associated with the apocrine secretion process of the endometrium. Recently it has been possible to dissociate the CA125 complex into its component substructure which indicates that CA125 epitopes are present on a 66kD, 97kD and 115kD subunits. It is the objective of this proposal to understand the role (or co-incidental expression) of CA125 in malignancy as well as the biology of the CA125 molecule in normal growth and development. To do so, and to provide the basis for such an understanding it is proposed to structurally analyze the purified subunits of the CA125 molecule and to develop both antibodies and sequence information for use as reagents to clone and characterize the CA125 gene(s).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040406-07
Application #
3180282
Study Section
Pathology B Study Section (PTHB)
Project Start
1986-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Arkansas for Medical Sciences
Department
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205

  Publications

Fendrick, J L; Konishi, I; Geary, S M et al. (1997) CA125 phosphorylation is associated with its secretion from the WISH human amnion cell line. Tumour Biol 18:278-89
de Groot, C J; O'Brien, T J; Taylor, R N (1996) Biochemical evidence of impaired trophoblastic invasion of decidual stroma in women destined to have preeclampsia. Am J Obstet Gynecol 175:24-9
Konishi, I; Fendrick, J L; Parmley, T H et al. (1994) Epidermal growth factor enhances secretion of the ovarian tumor-associated cancer antigen CA125 from the human amnion WISH cell line. J Soc Gynecol Investig 1:89-96
Fendrick, J L; Staley, K A; Gee, M K et al. (1993) Characterization of CA 125 synthesized by the human epithelial amnion WISH cell line. Tumour Biol 14:310-8
Burks, A W; Williams, L W; Connaughton, C et al. (1992) Identification and characterization of a second major peanut allergen, Ara h II, with use of the sera of patients with atopic dermatitis and positive peanut challenge. J Allergy Clin Immunol 90:962-9
O'Brien, T J; Raymond, L M; Bannon, G A et al. (1991) New monoclonal antibodies identify the glycoprotein carrying the CA 125 epitope. Am J Obstet Gynecol 165:1857-64
Burks, A W; Williams, L W; Helm, R M et al. (1991) Identification of a major peanut allergen, Ara h I, in patients with atopic dermatitis and positive peanut challenges. J Allergy Clin Immunol 88:172-9
Hardardottir, H; Parmley 2nd, T H; Quirk Jr, J G et al. (1990) Distribution of CA 125 in embryonic tissues and adult derivatives of the fetal periderm. Am J Obstet Gynecol 163:1925-31
O'Brien, T J; Bannon, G A; Bard, D S et al. (1989) Expression of the ras oncogene in gynecologic tumors. Am J Obstet Gynecol 160:344-52
Long, C A; O'Brien, T J; Sanders, M M et al. (1988) ras oncogene is expressed in adenocarcinoma of the endometrium. Am J Obstet Gynecol 159:1512-6

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