Chlorsulfuron resistance in Daucus carota cell lines and plants:Involvement of gene amplification

1994 ◽  
Vol 88 (5) ◽  
pp. 520-524 ◽  
Author(s):  
S. Caretto ◽  
M. C. Giardina ◽  
C. Nicolodi ◽  
D. Mariotti
Keyword(s):  
Cell Lines ◽  
Gene Amplification ◽  
Daucus Carota ◽  
Chlorsulfuron Resistance

Biochemical Evidence for Two Forms of Acetohydroxyacid Synthase in Daucus carota L. Cell Lines Selected for Chlorsulfuron Resistance

1999 ◽  
Vol 64 (2) ◽  
pp. 76-84 ◽  
Author(s):  
Sofia Caretto ◽  
Maria Carmela Giardina ◽  
Antonella Macagnano ◽  
Elena Bray ◽  
Chiara Nicolodi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Daucus Carota ◽  
Acetohydroxyacid Synthase ◽  
Biochemical Evidence ◽  
Daucus Carota L ◽  
L Cell ◽  
Chlorsulfuron Resistance

Mathematical models of gene amplification with applications to cellular drug resistance and tumorigenicity.

Genetics ◽  
1990 ◽  
Vol 125 (3) ◽  
pp. 633-644
Author(s):  
M Kimmel ◽  
D E Axelrod
Keyword(s):  
Mathematical Models ◽  
Cell Lines ◽  
Gene Amplification ◽  
Dihydrofolate Reductase ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Published Data ◽  
Reductase Gene ◽  
Double Minute ◽  
Double Minute Chromosomes

Abstract An increased number of copies of specific genes may offer an advantage to cells when they grow in restrictive conditions such as in the presence of toxic drugs, or in a tumor. Three mathematical models of gene amplification and deamplification are proposed to describe the kinetics of unstable phenotypes of cells with amplified genes. The models differ in details but all assume probabilistic mechanisms of increase and decrease in gene copy number per cell (gene amplification/deamplification). Analysis of the models indicates that a stable distribution of numbers of copies of genes per cell, observed experimentally, exists only if the probability of deamplification exceeds the probability of amplification. The models are fitted to published data on the loss of methotrexate resistance in cultured cell lines, due to the loss of amplified dihydrofolate reductase gene. For two mouse cell lines unstably resistant to methotrexate the probabilities of amplification and deamplification of the dihydrofolate reductase gene on double minute chromosomes are estimated to be approximately 2% and 10%, respectively. These probabilities are much higher than widely presumed. The models explain the gradual disappearance of the resistant phenotype when selective pressure is withdrawn, by postulating that the rate of deamplification exceeds the rate of amplification. Thus it is not necessary to invoke a growth advantage of nonresistant cells which has been the standard explanation. For another analogous process, the loss of double minute chromosomes containing the myc oncogene from SEWA tumor cells, the growth advantage model does seem to be superior to the amplification and deamplification model. In a more theoretical section of the paper, it is demonstrated that gene amplification/deamplification can result in reduction to homozygosity, such as is observed in some tumors. Other applications are discussed.

Amplification and expression of the TGF-α, EGF receptor and c-myc genes in four human oesophageal squamous cell carcinoma lines

1993 ◽  
Vol 13 (5) ◽  
pp. 303-312 ◽  
Author(s):  
Gregory J. Jones ◽  
Nina S. Heiss ◽  
Robin B. Veale ◽  
Alan L. Thornley
Keyword(s):  
Squamous Cell Carcinoma ◽  
Growth Factor ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Gene Amplification ◽  
Squamous Cell ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Scatchard Analysis ◽  
Oesophageal Squamous Cell Carcinoma

We have previously shown that four human oesophageal squamous cell carcinoma (SCC) cell lines secrete significant quantities of transforming growth factor alpha (TGF-α) in vitro. Three of these lines are known to produce supernumary low-affinity epidermal growth factor receptors (EGF-Rs). Using an125I-EGF compeitive binding assay and Scatchard analysis, we show that the fourth also overproduces low-affinity receptors. According to slot blot DNA analyses, the secretion of high levels of TGF-α is not associated with amplification of the TGF-α gene, and hyperproduction of the EGF-R is correlated with receptor gene amplification. Western blot analyses show that the c-Myc protein is overexpressed in two of the cell lines; and Southern and Northern blot analyses indicate that this overexpression occurs independently of c-myc gene amplification. Our results are consistent with an autocrine role for TGF-α and EGF-R in oesophageal carcinogenesis and support the possibility that c-myc overexpression may be required for the in vivo tumourigenicity of cells that produce high levels of TGF-α and the EGF-R.

scholarly journals Human tumor cell lines with EGF receptor gene amplification in the absence of aberrant sized mRNAs

1985 ◽  
Vol 13 (23) ◽  
pp. 8477-8486 ◽  
Author(s):  
C.Richter King ◽  
Matthias H. Kraus ◽  
Lewis T. Williams ◽  
Glenn T. Merlino ◽  
Ira H. Pastan ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Gene Amplification ◽  
Egf Receptor ◽  
Receptor Gene ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

scholarly journals Packaging Cells Based on Inducible Gene Amplification for the Production of Adeno-Associated Virus Vectors

1998 ◽  
Vol 72 (9) ◽  
pp. 7024-7031 ◽  
Author(s):  
Naoki Inoue ◽  
David W. Russell
Keyword(s):  
Cell Lines ◽  
Gene Amplification ◽  
Large Scale ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Scale Production ◽  
Adeno Associated Virus ◽  
Tetracycline Transactivator ◽  
Producer Cell

ABSTRACT Although vectors based on adeno-associated virus (AAV) offer several unique advantages, their usage has been hampered by the difficulties encountered in vector production. In this report, we describe a new AAV packaging system based on inducible amplification of integrated helper and vector constructs containing the simian virus 40 (SV40) replication origin. The packaging and producer cell lines developed express SV40 T antigen under the control of the reverse tetracycline transactivator system, which allows inducible amplification of chromosomal loci linked to the SV40 origin. Culturing these cells in the presence of doxycycline followed by adenovirus infection resulted in helper and vector gene amplification as well as higher vector titers. Clonal producer cell lines generated vector titers that were 10 times higher than those obtained by standard methods, with approximately 104vector particles produced per cell. These stocks were free of detectable replication-competent virus. The lack of a transfection step combined with the reproducibility of stable producer lines makes this packaging method ideally suited for the large-scale production of vector stocks for human gene therapy.

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