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Acquisition and loss of amplified genes: dramatic effects of hormones, tumor promoters and cytotoxic drugs

Varshavsky, A. and Barsoum, J. and Roninson, I. and Snapka, R. (1983) Acquisition and loss of amplified genes: dramatic effects of hormones, tumor promoters and cytotoxic drugs. Princess Takamatsu symposia, 14 . pp. 235-254. https://resolver.caltech.edu/CaltechAUTHORS:20201125-154028200

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Abstract

We discuss our recent findings in three related areas of the gene amplification field. 1) We have found that tumor-promoting phorbol esters, nonphorbol tumor promoters, and most significantly, mitogenic hormones, such as insulin, vasopressin, and epidermal growth factor (EGF), greatly increase the incidence of methotrexate (MTX) resistance in 3T6 cells under condition of MTX selection. Most of these MTX-resistant cells bear amplified dihydrofolate reductase (DHFR) genes. 2) We have discovered that when mouse cells bearing unstably amplified DHFR genes are grown in the presence of nonlethal concentrations of hydroxyurea (HU), the rate of loss of the DHFR genes from these cells is greatly increased. 3) We have developed a new method for detection and mapping of homologous, repeated and amplified DNA sequences, and have used this method to detect and clone amplified DNA fragments in mammalian cells resistant simultaneously to a number of different drugs.


Item Type:Article
ORCID:
AuthorORCID
Varshavsky, A.0000-0002-4011-258X
Record Number:CaltechAUTHORS:20201125-154028200
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201125-154028200
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ID Code:106833
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:11 Dec 2020 16:36
Last Modified:11 Dec 2020 16:36

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