This project seeks to gain an understanding of some of the mechanisms involved in growth control in 'normal' cultured mammalian cells and to describe some of the metabolic and regulatory consequences of oncogene expression in cultured cells. Tumor cells differ from normal cells in the regulation of cell proliferation and cell differentiation; much recent evidence suggests that these differences stem from inappropriate expression of specific DNA sequences or oncogenes. The gene products of a substantial number of these oncogenes have been identified and characterized but there is considerable uncertainty about the function of these proteins in cells. Since the loss of growth control associated with oncogene expression reflects an alteration of the normal mechanisms of growth regulation it is important to examine those mechanisms in a normal, untransformed cell as a control for the transformed cell. In the work proposed, we intend to contribute to an understanding of this subject by applying NMR to study the correlates of a transition from quiescence to growth elicited by mitogenic stimulation of mouse fibroblast 3T3 cells. The parameters which have been reported to be affected by such stimuli include among others; an increase in ion fluxes, an increase in intracellular pH and an increase in the intracellular content of a number of cations, most significantly Na+, K+ and Ca++. These parameters are accessible to study with NMR spectroscopy which being a noninvasive and nondestructive technique offers very significant advantages over other techniques utilized in the study of these phenomena. Thus far we have developed methodologies which allow us to obtain unique information on intracellular pH, and while we further pursue such studies, we intend to refine and elaborate methodologies to observe and study the other parameters mentioned above. With these new methodologies and with reference set of data on the untransformed 3T3 cell line, we intend to extend our studies to cell lines derived from the 3T3 cells by transformation with specific oncogenes such as src and ras and possibly to other cell lines such as those derived from tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA041078-02
Application #
3820793
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Fox Chase Cancer Center
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Lee, Seung-Cheol; Arias-Mendoza, Fernando; Poptani, Harish et al. (2012) Prediction and Early Detection of Response by NMR Spectroscopy and Imaging. PET Clin 7:119-26
Hultman, Kristi L; Raffo, Anthony J; Grzenda, Adrienne L et al. (2008) Magnetic resonance imaging of major histocompatibility class II expression in the renal medulla using immunotargeted superparamagnetic iron oxide nanoparticles. ACS Nano 2:477-84
Stoyanova, Radka; Querec, Troy D; Brown, Truman R et al. (2004) Normalization of single-channel DNA array data by principal component analysis. Bioinformatics 20:1772-84
Stoyanova, Radka; Nicholls, Andrew W; Nicholson, Jeremy K et al. (2004) Automatic alignment of individual peaks in large high-resolution spectral data sets. J Magn Reson 170:329-35
Stoyanova, Radka; Nicholson, Jeremy K; Lindon, John C et al. (2004) Sample classification based on Bayesian spectral decomposition of metabonomic NMR data sets. Anal Chem 76:3666-74
Sajda, Paul; Du, Shuyan; Brown, Truman R et al. (2004) Nonnegative matrix factorization for rapid recovery of constituent spectra in magnetic resonance chemical shift imaging of the brain. IEEE Trans Med Imaging 23:1453-65
Nahum, Alan E; Movsas, Benjamin; Horwitz, Eric M et al. (2003) Incorporating clinical measurements of hypoxia into tumor local control modeling of prostate cancer: implications for the alpha/beta ratio. Int J Radiat Oncol Biol Phys 57:391-401
Stoyanova, R; Brown, T R (2002) NMR spectral quantitation by principal component analysis. III. A generalized procedure for determination of lineshape variations. J Magn Reson 154:163-75
Stoyanova, R; Brown, T R (2001) NMR spectral quantitation by principal component analysis. NMR Biomed 14:271-7
Ochs, M F; Stoyanova, R S; Arias-Mendoza, F et al. (1999) A new method for spectral decomposition using a bilinear Bayesian approach. J Magn Reson 137:161-76

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