It is proposed to use mouse salivary glands as an in vivo model to corroborate the hypothesis that proto-oncogenes play key roles in the regulation of differentiation and cell proliferation. To this end, we will analyze the expression of c-fos, c-myc, c-ras-Ki, and c-ras-Ha by measuring steady state levels of their transcripts by Northern and dot blot hybridization, transcriptional activities by nuclear run-off assays, the cellular population in which c-onc mRNAs are located by in situ hybridization, and the expression and location of c-onc proteins in salivary glands of the mouse by immunocytochemical methods. We will correlate c-onc expression with differentiation of the acinar cells in the parotid gland, quantitated by measuring the expression of the yield-amylase gene, with normal and isoproterenol-induced cell replication, and hyperplastic/hypertrophic growth produced by the chronic adminsitration of IPR. In preliminary experiments we have observed an early stimulation of c-fos expression by IPR. We propose to test the hypothesis that isoproterenol-induced c-fos expression in the salivary glands is mediated by cyclic AMP, and is independent of the secretory response of the acinar cells to IPR and other drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE007637-02
Application #
3221306
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1986-04-01
Project End
1989-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Barka, T; Asbell, P A; van der Noen, H et al. (1991) Cystatins in human tear fluid. Curr Eye Res 10:25-34
Shaw, P A; Barka, T; Woodin, A et al. (1990) Expression and induction by beta-adrenergic agonists of the cystatin S gene in submandibular glands of developing rats. Biochem J 265:115-20
Barka, T; van der Noen, H; Gresik, E W (1989) Adrenergic regulation of c-fos expression in cultured BC3H1 muscle cells. Exp Cell Res 185:419-35
Shaw, P A; Barka, T (1989) Beta-adrenergic induction of a cysteine-proteinase-inhibitor mRNA in rat salivary glands. Biochem J 257:685-9
Shaw, P A; Cox, J L; Barka, T et al. (1988) Cloning and sequencing of cDNA encoding a rat salivary cysteine proteinase inhibitor inducible by beta-adrenergic agonists. J Biol Chem 263:18133-7
Barka, T; van der Noen, H; Shaw, P A (1987) Proto-oncogene fos (c-fos) expression in the heart. Oncogene 1:439-43
Morrell, J I; Gresik, E W; Barka, T (1987) Autoradiographic localization of dihydrotestosterone binding in the major salivary glands and other androgen-responsive organs of the mouse. J Histochem Cytochem 35:1053-8
Barka, T; Gubits, R M; van der Noen, H (1987) Accumulation of c-fos mRNA in slices of mouse submandibular gland incubated in vitro. Oncogene 1:297-300
Yagil, C; Naito, Y; Barka, T (1986) Immunocytochemical localization of a developmentally regulated, isoproterenol-inducible protein (LM protein) in rat submandibular gland. Am J Anat 177:55-62
Barka, T; Gubits, R M; van der Noen, H M (1986) Beta-adrenergic stimulation of c-fos gene expression in the mouse submandibular gland. Mol Cell Biol 6:2984-9