Abstract

The long-term objective of this application is to identify differences in growth regulation between neoplastic and nonneoplastic cells that can be exploited in improving chemotherapy in man. Our first goal is to determine whether increases in the concentration of free intracellular calcium are important in growth regulation of neoplastic and nonneoplastic cells.
Our specific aims i nclude: (1) determining whether an intracellular microinjection of calcium can produce events leading toward DNA synthesis; and (2) using the introduction of Aequorin, Quin 2, and FURA 2 into cells to determine whether growth factors do indeed produce an increase in the concentration of free intracellular calcium. We will monitor changes in centriole events by indirect immunofluorescence using anti-tubulin antibody and by electron microscopy. DNA synthesis will be followed by autoradiography using tritiated thymidine. Eventually these projects will allow us to ask how the role of intracellular calcium is different in the growth of nonneoplastic (3T3) and neoplastic cells (SV3T3 or 3T12). (J)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA034472-02
Application #
3172199
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Tucker, R W; Fay, F S (1990) Distribution of intracellular free calcium in quiescent BALB/c 3T3 cells stimulated by platelet-derived growth factor. Eur J Cell Biol 51:120-7
Hennings, H; Kruszewski, F H; Yuspa, S H et al. (1989) Intracellular calcium alterations in response to increased external calcium in normal and neoplastic keratinocytes. Carcinogenesis 10:777-80
Tucker, R W; Chang, D T; Meade-Cobun, K (1989) Effects of platelet-derived growth factor and fibroblast growth factor on free intracellular calcium and mitogenesis. J Cell Biochem 39:139-51
Ho, P T; Tucker, R W (1989) Centriole ciliation and cell cycle variability during G1 phase of BALB/c 3T3 cells. J Cell Physiol 139:398-406
Rowinsky, E K; Donehower, R C; Jones, R J et al. (1988) Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. Cancer Res 48:4093-100
Fay, F S; Williams, D A; Kargacin, G et al. (1988) Role of local [Ca+2] in the control of cell function. Adv Exp Med Biol 232:213-9