Biomaterial Database

A 12-O-tetradecanoylphorbol-13-acetate (TPA)-nonproliferative variant of 3T3 cells is resistant to TPA-enhanced gene amplification. 1985

H R Herschman

Barsoum and Varshavsky (Proc. Natl. Acad. Sci. U.S.A. 80:5330-5334, 1983) suggest that polypeptide mitogens and the mitogenic tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulate gene amplification by related pathways. I demonstrated that TPA and the polypeptide mitogen fibroblast growth factor (FGF) both increase the frequency of cadmium-resistant variants of Swiss-Webster 3T3 cells. The molecular basis for this phenomenon is the amplification of the metallothionein gene(s). To further characterize the relationship between mitogenesis and gene amplification, I examined the ability of TPA and FGF to increase the frequency of cadmium-resistant colonies in the 3T3 variant cell line 3T3-TNR9. Unlike 3T3 cells, 3T3-TNR9 cells cannot be stimulated by TPA to divide (E. Butler-Gralla and H. R. Herschman, J. Cell. Physiol. 107:59-68, 1981). TPA does not induce an increase in cadmium-resistant colonies of the TPA-nonproliferative 3T3-TNR9, variant, in contrast to its efficacy on 3T3 cells. FGF, a potent mitogen for 3T3-TNR9 cells as well as 3T3 cells, is equally effective for 3T3-TNR9 and 3T3 cells in inducing cadmium-resistant colonies. These data suggest that the pathways of TPA-induced gene amplification and TPA-stimulated mitogenesis share a common step(s). TPA caused transient inhibition of DNA synthesis in both dividing 3T3 and 3T3-TNR9 cells, suggesting that this latter response to TPA is not sufficient to enhance gene amplification.

UI	MeSH Term	Description	Entries
D008938	Mitosis	A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.	M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010704	Phorbols	The parent alcohol of the tumor promoting compounds from CROTON OIL (Croton tiglium).	Tigliane,Tiglianes
D002104	Cadmium	An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D005784	Gene Amplification	A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.	Amplification, Gene
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia