Abstract

An experimental model of human endometrial carcinoma has been developed, in which human tumors are grown and passaged in nude mice with maintenance of their biochemical and morphological characteristics. The progesterone receptor has been characterized and partially purified from tumors grown in nude mice, and monoclonal antibodies have been prepared. These experimental tools, and the ability to sensitively modulate the progesterone receptor in this experimental system place us in an ideal position to study the physicochemical characteristics of purified progesterone receptor proteins, which in turn, will serve as the basis for comparison with the altered characteristics of these proteins during the regulation of progesterone receptor in vivo. Therefore, the specific aims of this proposal are 1) to study the structure of human endometrial carcinoma PR 2) to investigate the regulation of PR structure, 3) to determine the relationship between PR structure and biological response and 4) to analyze the mechanism of down regulation of PR by progestins. These studies will significantly advance our understanding of the biology of progestin action in endometrial carcinoma which is the longterm objective of this proposal.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA046349-04
Application #
3189597
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1989-07-01
Project End
1993-12-31
Budget Start
1992-01-01
Budget End
1992-12-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033

  Publications

Lin, J; Lei, Z M; Lojun, S et al. (1994) Increased expression of luteinizing hormone/human chorionic gonadotropin receptor gene in human endometrial carcinomas. J Clin Endocrinol Metab 79:1483-91
Satyaswaroop, P G (1993) Development of a preclinical model for hormonal therapy of human endometrial carcinomas. Ann Med 25:105-11
Tabibzadeh, S; Sun, X Z; Kong, Q F et al. (1993) Induction of a polarized micro-environment by human T cells and interferon-gamma in three-dimensional spheroid cultures of human endometrial epithelial cells. Hum Reprod 8:182-92
Satyaswaroop, P G; Clarke, C L; Zaino, R J et al. (1992) Apparent resistance in human endometrial carcinoma during combination treatment with tamoxifen and progestin may result from desensitization following downregulation of tumor progesterone receptor. Cancer Lett 62:107-14
Sakakibara, K; Kan, N C; Satyaswaroop, P G (1992) Both 17 beta-estradiol and tamoxifen induce c-fos messenger ribonucleic acid expression in human endometrial carcinoma grown in nude mice. Am J Obstet Gynecol 166:206-12
Satyaswaroop, P G; Tabibzadeh, S S (1991) Extracellular matrix and the patterns of differentiation of human endometrial carcinomas in vitro and in vivo. Cancer Res 51:5661-6
Schneider, W; Ramachandran, C; Satyaswaroop, P G et al. (1991) Murine progesterone receptor exists predominantly as the 83-kilodalton 'A' form. J Steroid Biochem Mol Biol 38:285-91
Mortel, R; Zaino, R J; Satyaswaroop, P G (1990) Designing a schedule of progestin administration in the control of endometrial carcinoma growth in the nude mouse model. Am J Obstet Gynecol 162:928-34;discussion 934-6
Satyaswaroop, P G; Mortel, R (1990) Hormonal treatment of endometrial carcinoma: an overview and new development in biology. J Steroid Biochem Mol Biol 37:997-1001
Tabibzadeh, S S; Sivarajah, A; Carpenter, D et al. (1990) Modulation of HLA-DR expression in epithelial cells by interleukin 1 and estradiol-17 beta. J Clin Endocrinol Metab 71:740-7

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