(A) Outline of the malignant transformation process.

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(A) Outline of the malignant transformation process. (A) Outline of the malignant transformation process. Schematic representation of the spontaneous (young, senescent, immortal, tumorigenic, INK4A methylation) and induced (hTERT, H‐Ras, p53 inactivation) modifications of the WI‐38 cells along the process of malignant transformation. The stages chosen for microarray profiling are indicated by boxes with numerals corresponding to columns in the expression matrix shown in (B). The time scale of the process is depicted by a horizontal axis, and the corresponding population doublings are represented by PDLs. (B) The normalized expression levels of the 168 genes in the proliferation cluster at 12 stages spanning the transformation process. Normalized expression level is color‐coded according to the color bar on the right. The table below the matrix contains the following information on each sample: days in culture, geometric mean and standard deviation of expression level of the cluster's genes, doubling rate (cell cycle doublings/day) of cells at selected stages, activity of hTERT (designated as ‘+’ for all samples following hTERT overexpression), activity of p53, as inferred from the application of its dominant‐negative peptide, GSE56 (‘−’ indicates expression of GSE56). Here and throughout the paper, the following cell line designations are introduced: cells are either young or senescent; grow slow or fast; a sample name followed by ‘G’ denotes the application of GSE56; T before sample names indicates the presence of the immortalizing telomerase; R following the sample name indicates the insertion of Ras. Yuval Tabach et al. Mol Syst Biol 2005;1:2005.0022 © as stated in the article, figure or figure legend