Open AccessSelective nature of phorbol 12-myristate 13-acetate-induced neoplastic transformation in NIH 3T3 cells.
Author(s) -
Andrew L. Rubin,
Harry Rubin
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.6.2320
Subject(s) - transformation (genetics) , neoplastic transformation , 3t3 cells , malignant transformation , phorbol , cell culture , biology , transformation efficiency , incubation , biochemistry , chemistry , microbiology and biotechnology , transfection , genetics , phosphorylation , carcinogenesis , gene , protein kinase c , agrobacterium
The ability of phorbol 12-myristate 13-acetate (PMA) at 0.02 microgram/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 original cells were grown in 2% calf serum (CS) and exposed continually to PMA for at least 4 weeks before transfer into the assay. Transformation 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 PMA-enhanced 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 maximizing 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 PMA-enhanced transformation.