We are attempting to gain insight into the biologic and biochemical events that determine and regulate tissue-specific gene expression and the alterations that accompany or follow neoplastic transformation. Four biologic systems exemplifying differential gene expression are under study. Alpha 2u globulins are a gene family manifesting tissue-specific gene expression which ceases upon neoplastic transformation. Alternate processing sites within intron six have been detected. The 7 kb gene has seven exons, a (GT)27 repeat sequence flanked by enhancer sequences as well as a 5' glucocorticoid receptor consensus sequence. Members of this gene family have been inserted into transgenic mice and transfected into various cell lines to study the relationship between gene structure, development, and tissue-specific gene expression. Cell-free transcriptional and binding studies are attempting to identify tissue-specific transcriptional regulators. Enhancers and tissue specific transacting proteins as determinants of tissue-specific immunoglobulin gene expression are being investigated. Deletions and exchange of putative regulatory regions followed by transfection into various cell types may identify regulatory regions. Translational inhibitors may determine the degree to which proteins modulate gene expression. Dopamine agonist regulation of transcription of selected members of the kallikrein gene family is being examined. cDNAs of expressed kallikrein genes have been isolated from a lambda GT10 pituitary library. In vitro nuclear transcription and tissue levels of kallikrein mRNA will be evaluated. Experiments are continuing to isolate cDNAs to the alpha and beta subunits of the hormone inducible Na/K ATPase. Transfected fibroblasts contain two Na/K ATPases, one of which has low affinity for and is resistant to ouabain. (V)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA022376-11
Application #
3092972
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1979-09-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Son, H J; Shahan, K; Derman, E et al. (1991) Expression of a silent MUP gene in transgenic mice. Biotechnology 16:75-80
Perfetti, V; Borden, P; Tao, M H et al. (1991) Specificity and variable region cDNA sequence of an isogeneic monoclonal antiidiotype to an anti-alpha(1----6)dextran. Mol Immunol 28:505-15
Gick, G G; Melikian, J; Ismail-Beigi, F (1990) Thyroidal enhancement of rat myocardial Na,K-ATPase: preferential expression of alpha 2 activity and mRNA abundance. J Membr Biol 115:273-82
Gick, G G; Ismail-Beigi, F (1990) Thyroid hormone induction of Na(+)-K(+)-ATPase and its mRNAs in a rat liver cell line. Am J Physiol 258:C544-51
Pachnis, V; Pevny, L; Rothstein, R et al. (1990) Transfer of a yeast artificial chromosome carrying human DNA from Saccharomyces cerevisiae into mammalian cells. Proc Natl Acad Sci U S A 87:5109-13
Dwivedi, R S; Yeldandi, A V; Subbarao, V et al. (1990) Androgen regulated expression of the alpha 2u-globulin gene in pancreatic hepatocytes of rat. J Cell Biol 110:263-7
Cayanis, E; Bayley, H; Edelman, I S (1990) Cell-free transcription and translation of Na,K-ATPase alpha and beta subunit cDNAs. J Biol Chem 265:10829-35
Sarkar, P; Feigelson, P (1989) Developmentally regulated male-specific transfactor(s) enable in vitro transcription of a cloned alpha 2u-globulin gene. Mol Endocrinol 3:342-8
Choy, H A; McLaughlin, M; Feigelson, P (1989) Nuclear factors from expressing tissues interact in vitro with a rat alpha-2u globulin gene intron. J Biol Chem 264:1754-9
Morrison, S L; Oi, V T (1989) Genetically engineered antibody molecules. Adv Immunol 44:65-92

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