Awardee OrganizationUNIV OF NORTH CAROLINA CHAPEL HILL
Description
Abstract Text
We have found that there is a striking difference between normal, diploid
cells and tumorigenic ell in their ability to amplify a given endogenous
gene. Amplification frequency is high in tumorigenic cells (10-3), lower
in nontumorigenic, preneoplastic cells (10-5) and undetectable in normal,
diploid cells (lessor10-9). To investigate the genetic control of gene
amplification, amplification frequency was measured in hybrids formed
between tumorigenic cells and normal, diploid cells. The ability to
amplify an endogenous gene behaved as a recessive genetic trait.
Amplification frequency in the hybrid cells was suppressed by over five
orders of magnitude (10-3 to lessor10-8). We observed that diploid cells
that had not detectable frequency of gene amplification are arresting in
the cell cycle when placed in the metabolic inhibitor, PALA. Tumorigenic
cells do not arrest but proceed to make a choice between growth (containing
amplified target genes) or suicide, the activation of apoptosis. In this
application we wish to address two questions. 1) is there a functional
connection between the metabolic growth arrest in normal cells and their
ability to amplify? and 2) is apoptosis the default alternative? We will
approach these goals by examining the relationship between growth arrest
and amplification using flowcytometry as a method of detection we can
determine if the cellular arrest generates amplification intermediates. We
will also examine amplification of genes that are not directly connected to
the production of nucleotide precursors. Finally, we will ask if genes
that suppress amplification ability suppress apoptosis. We will use the
somatic cell hybrids we have characterized for these purposes.
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