A comparison of inducer mediated differentiation of HL60 cells and a TPA resistant derivative of the HL60 cell line.
Item
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Title
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A comparison of inducer mediated differentiation of HL60 cells and a TPA resistant derivative of the HL60 cell line.
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Identifier
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AAI8820850
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identifier
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8820850
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Creator
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Calderon, Tina Marie.
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Contributor
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Adviser: Judith K. Christman
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Date
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1988
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, General
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Abstract
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The HL60 cell line can be induced to differentiate along the myelocytic and monocytic developmental pathways and thus provides a model invitro system for the study of cellular differentiation. The HL60 T cell line, a derivative of the HL60 cell line, was isolated for its resistance to TPA and the effects of various inducing agents on both cell lines was studied in order to try to identify the biochemical events critical to the process of cellular differentiation.;The response of HL60 and HL60 T cells to inducing agents was found to be markedly different. HL60 T cells did not differentiate when exposed to a variety of known inducers. However, 13-Cis-retionic acid promoted the granulocytic maturation of these cells which revealed that the HL60 T cell line maintained the capacity to terminally differentiate.;The correlation between the ability of inducing agents to promote cellular differentiation and their effects on biochemical events that have been postulated to play an important role in the regulation of cellular differentiation were then examined. Experiments utilizing a variety of weak acids and bases failed to support the theory that transient cytoplasmic ion fluxes are a critical regulator of HL60 cell differentiation. The use of monoclonal antibodies that recognized lineage specific cell surface antigens confirmed the induction of granulocytic differentiation of HL60 cells by specific inducing agents and also identified a protein whose appearance was indicative of the responsiveness of HL60 cells to TPA.;Inducing agents were also shown to promote a decrease in S-Adenosylmethionine levels in both cell lines without affecting the pattern of 5-methylcytosine residues in DNA sequences coding for specific cellular oncogenes. Subsequent studies on the effects of inducing agents on the level of poly A+ RNA revealed the one major difference between the two cell lines. The HL60 T cell line maintains a much higher level of c-myb poly A+ RNA, implicating a major role for the expression of this cellular oncogene in the control of cellular differentiation.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
