Abstract

The overall goal of this proposal is to examine the structure, function and regulation of type II binding sites in normal and neoplastic cells. Type II binding sites are receptors for methyl-hydroxyphenylactate and are thought to be involved in the inhibition of cell proliferation. In order to accomplish this general goal the following specific aims are proposed. The type II binding site will be purified from chick oviduct and/or rat uterus. This will be done by size, charge and affinity chromatography. Purified type II antigen will be used to produce monocolonal and polyclonal antibodies. These will be use for qualitative and quantitative analyses of type Ii sites and the estrogen receptor. Antibodies to type II sites will also be use, along with oligonucleotide probes, to screen cDNA libraries for the type II gene. The gene will be characterized and the cDNA used as a pulse for the study of the regulate of type II site gene expression. Regulation of type Ii expression will be examined in achieving expression systems, transgenic mice, normal and neoplastic cells in culture and in intact and ovariectomized animal. These experiments should produce a much better understanding of the role of type Ii site expression and regulation in the biology of normal, estrogen regulated and neoplastic cell growth.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD008436-19
Application #
3310894
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1976-06-01
Project End
1994-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
19
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Garai, J; Clark, J H (1994) Estrogen affinity crosslinking to tyrosinase-like immunoreactive proteins of rat uterine nuclear extracts. J Steroid Biochem Mol Biol 49:161-5
Law, S W; Apostolakis, E M; Samora, P J et al. (1994) Hormonal regulation of hypothalamic gene expression: identification of multiple novel estrogen induced genes. J Steroid Biochem Mol Biol 51:131-6
Garai, J; Tiller, A A; Clark, J H (1992) Tyrosinase-like polypeptides in the uterus and in the central nervous system of rats. Steroids 57:183-8
Garai, J; Clark, J H (1992) Tyrosinase-like activity and estradiol binding in rat uterine nuclear extracts. Steroids 57:248-56
Markaverich, B M; Gregory, R R; Alejandro, M et al. (1990) Methyl p-hydroxyphenyllactate and nuclear type II binding sites in malignant cells: metabolic fate and mammary tumor growth. Cancer Res 50:1470-8
Klein-Hitpass, L; Tsai, S Y; Greene, G L et al. (1989) Specific binding of estrogen receptor to the estrogen response element. Mol Cell Biol 9:43-9
Densmore, C L; Markaverich, B M; O'Malley, B W et al. (1989) Characterization and partial purification of an estrogen type II binding site in chick oviduct cytosol. Biochemistry 28:7788-96
Markaverich, B M; Roberts, R R; Alejandro, M A et al. (1988) Bioflavonoid interaction with rat uterine type II binding sites and cell growth inhibition. J Steroid Biochem 30:71-8
Markaverich, B M; Gregory, R R; Alejandro, M A et al. (1988) Methyl p-hydroxyphenyllactate. An inhibitor of cell growth and proliferation and an endogenous ligand for nuclear type-II binding sites. J Biol Chem 263:7203-10
Clark, J H; Mitchell, W C; Guthrie, S C (1987) Triphenylethylene antiestrogen binding sites (TABS) specificity. J Steroid Biochem 26:433-7

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