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Spontaneous and 5-azacytidine-induced revertants of methionine-dependent tumor-derived and H-ras-1-transformed cells.

par Vanhamme, Luc ;Szpirer, Claude
Référence Experimental cell research, 181, 1, page (159-168)
Publication Publié, 1989-03

Article révisé par les pairs

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Résumé :

Methionine dependence is a metabolic defect affecting several tumor-derived and transformed cell lines; it is defined as the inability of cells to grow in a medium where methionine has been depleted and replaced by its immediate metabolic precursor, homocysteine. This defect is acquired by normal epithelial Clone 9-3 cells upon transformation by the activated H ras-1 oncogene. We report that these H-ras-1-transformed cells (as well as some other tumor or transformed cells) spontaneously revert to methionine dependence at a high frequency. These revertants still express the H-ras-1 oncogene and retain their anchorage-independent growth: this reversion is thus not associated with a complete reversion to the normal phenotype. Furthermore, the reversion frequency is dramatically increased (up to 400-fold) by treatment of the cells with 5-azacytidine, a strong demethylating agent. Methionine dependence might thus be a consequence of hypermethylation of a critical gene involved in methionine metabolism and possibly in the methylation processes themselves.