Two-stage malignant transformation in hamster embryo cells

Poiley, J. A.; Raineri, R.; Pienta, Roman J.

doi:10.1038/bjc.1979.2

Cited by 21 publications

(7 citation statements)

References 7 publications

(6 reference statements)

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“…The phorbol ester TPA has been shown to promote transformation in fibroblasts after carcinogen treatment in vitro (Lasne et al, 1974;Mondal et al, 1976;Poiley, 1979) and also to affect a number of cell properties in culture independently of carcinogen treatment (Weinstein et al, 1977). One of the changes demonstrated was increased PA activity (Wigler & Weinstein, 1976).…”

Section: Discussionmentioning

confidence: 99%

“…The results showed that TPA did not accelerate the acquisition of either property. However, TPA enhanced the levels of PA activity once this had started to rise ( (Wigler & Weinstein, 1976 (Poiley et al, 1979;Mondal et al, 1976;Lasne et al, 1974). However, it could be that TPA cannot affect the rate of acquisition of transformed properties in this system in which ENU is the carcinogen, as the results so far suggest (see also below).…”

Section: Discussionmentioning

confidence: 99%

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Effect of 12-O-tetradecanoylphorbol-13-acetate on two charateristics of transformation acquired sequentially by ENU-exposed rat brain cells

Roscoe¹,

Hince²,

Claisse³

et al. 1980

Br J Cancer

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Summary.-Cultures derived from rat brains at different times during the latent period of brain-tumour induction by N-ethyl-N-nitrosourea (ENU) showed increased plasminogen activator (PA) activity before being able to form colonies in agar. Control cultures from buffer-exposed animals showed neither property at comparable passages. More detailed investigations, using a culture derived from foetal brains only 2 days after exposure to ENU and clones from this culture, showed a sequence of low PA activity, then increased activity, followed by the ability to form colonies in agar, suggesting progressive transformation of cells in culture. Continuous culturing in the presence of the mouse skin tumour promoter, 12-0-tetradecanoylphorbol-13-acetate (TPA), did not accelerate the rate at which these two properties were acquired, but did cause a much greater increase of PA activity once this started to rise. If included in the assay mixture TPA also increased the PA activity of the cells. It therefore appears that in this system TPA can modulate PA activity under certain circumstances.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of 12-O-tetradecanoylphorbol-13-acetate on two charateristics of transformation acquired sequentially by ENU-exposed rat brain cells

Roscoe¹,

Hince²,

Claisse³

et al. 1980

Br J Cancer

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“…The basic protocol used was similar to one described by Poiley et al [11] and is outlined in figure 1. 3-Methylcholanthrene (MCA) was dissolved in acetone to a concentration of 0.5 mg/ml, and the stock solution was used at a dilution of 0.1% in DMEM + 10% NBCS to give a final concentration of 0.5 pg/ml.…”

Section: Transformation Assaymentioning

confidence: 99%

Inhibition of Chemically Induced Neoplastic Transformation in vitro by Saturated Fatty Acids

Embleton

Noy²

1991

Pathobiology

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Syrian hamster embryo cells were treated for 2–4 days with 3-methylcholanthrene (MCA), and 28 days after application of the carcinogen they were exposed continuously to 12-O-tetradecanoylphorbol-13-acetate (TPA). Untreated cells, or cells treated with MCA or TPA only, usually became senescent around 6–8 weeks after plating and died, but those treated with both MCA and TPA became immortalised and underwent transformation to a phenotype capable of growth in soft agar. Transformation was inhibited by derivatives of stearic acid administered to the cells at various stages of the overall process. Some derivatives were active at lower concentrations than others, but none were selective for specific phases such as initiation or promotion, and it did not appear to matter whether the fatty acids were present throughout the assay or for only part of it. Their action seems to be associated with control of growth or differentiation in a relatively non-specific manner.

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“…Strict correlations between these shortterm responses and the classic long-term response, tumor promotion in the skin ofmice, have been difficult to establish, particularly in view of the extremely divergent types of responses observed in cell culture. Both suppression and enhancement by phorbol 12-myristate 13-acetate (PMA) are observed in several systems depending, at least to some degree, on the amount of time elapsed between treatments with the initiating carcinogen and PMA (2,3). Changes in the nature of the cellular response to PMA invite speculation about the role of the metabolic state in mediating these responses.…”

mentioning

confidence: 99%

Selective nature of phorbol 12-myristate 13-acetate-induced neoplastic transformation in NIH 3T3 cells.

Rubin¹,

Rubin²

1994

Proc. Natl. Acad. Sci. U.S.A.

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The ability of phorbol 12-myristate 13-acetate (PMA) at 0.02 jpg/ml to induce neoplastic transformation in NIH 3T3 cells is highly dependent on the culture conditions. Optimal transformation, indicated by the saturation density and extent of focus formation in transferred cultures raised under standard conditions, was observed when the ornal cells were grown in 2% calf serum (CS) and exposed continually to PMA for at least 4 weeks before transfer into the assay. Transormation of stationary cultures in 10% CS occurred later and to a lesser degree than in 2% CS. The same cells subjected to thrice-weekly transfer in 2% or 10% CS at low cell density so that they were in a constant state of exponential growth exhibited no evidence of transformation in response to PMA. This strong condition-dependence of PMAenhanced transformation is indicative of a selection process similar to that described for spontaneous transformation. In both cases, transformation is promoted by inhibiting multiplication and prevented by zing multiplication. Therefore, it has the earmarks of an epigenetic rather than a mutational process and requires phenotypic rather than genotypic variation to supply the states for selection. The concept of "progressive state selection," originally proposed to account for spontaneous transformation, can also account for PMAenhnced transformation.Phorbol esters induce a wide spectrum of short-term responses in various cell culture systems. Such responses include changes in morphology, enzyme activities, ion transport, nutrient transport, and effects on saturation density, among others (for a review of the effects of promoters in cell culture, see ref. 1). Strict correlations between these shortterm responses and the classic long-term response, tumor promotion in the skin ofmice, have been difficult to establish, particularly in view of the extremely divergent types of responses observed in cell culture. Both suppression and enhancement by phorbol 12-myristate 13-acetate (PMA) are observed in several systems depending, at least to some degree, on the amount of time elapsed between treatments with the initiating carcinogen and PMA (2, 3). Changes in the nature of the cellular response to PMA invite speculation about the role of the metabolic state in mediating these responses.NIH 3T3 cells first came to wide attention as transformable recipients of ras oncogene sequences (4, 5). Studies conducted over the last several years have revealed, however, that these cells undergo spontaneous transformation in the absence of exogenous oncogenes in a manner that is dependent on environmental conditions (6,7). For example, exposure to growth constraints, such as those that occur at confluence or in low concentrations of serum, will induce transformation (8). High concentrations of glutamine, an important energy source for cultured cells, are required to obtain maximal transformation (9). Maintenance of transformed cells at low densities in high serum concentrations results in the gradual reversal of transformation a...

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Two-stage malignant transformation in hamster embryo cells

Cited by 21 publications

References 7 publications

Effect of 12-O-tetradecanoylphorbol-13-acetate on two charateristics of transformation acquired sequentially by ENU-exposed rat brain cells

Effect of 12-O-tetradecanoylphorbol-13-acetate on two charateristics of transformation acquired sequentially by ENU-exposed rat brain cells

Inhibition of Chemically Induced Neoplastic Transformation in vitro by Saturated Fatty Acids

Selective nature of phorbol 12-myristate 13-acetate-induced neoplastic transformation in NIH 3T3 cells.

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