HPV16 E7 Protein and hTERT Proteins Defective for Telomere Maintenance Cooperate to Immortalize Human Keratinocytes
Figure 5
E6, hTERTwt, and hTERT-D868A alter the expression of overlapping gene sets, including chromatin remodeling genes such as Bmi1.
Primary HFKs were stably transduced with either E6, hTERTwt, hTERT-D868A or puro babe control vector. Samples were submitted for whole genome expression array analysis (Figure S3). Expression profile changes shown by hTERTwt are compared to expression profile changes in E6 (A) and hTERT-D868A mutant (B). As expected, a significant amount of the expression changes seen in E6 (6991 total changes) were also altered by hTERT wt (1379, representing 20% of the E6 changes). Conversely, more than half of the hTERT changes (58%, 1379 of 2359 changes) were also seen by E6. Interestingly, of the 2359 genes altered by hTERTwt, 2077 of them (88%) were also altered by the hTERTci mutant (fold change >1.33 and p value <0.01). (C) 1258 changes were shared by E6, hTERTwt, and hTERT-D868A, including Bmi1. (D) Numerical fold change values are shown for all arrays as they correspond to two probes, NM_005180 and L13689. These accession numbers represent Bmi1 mRNA sequences that are 99% identical. Quantitative RT-PCR was performed on the E6 and hTERTwt or hTERT-D868A (E) with gene-specific primers for Bmi1 to validate the array results, normalized to GAPDH. n = 3. Bars represent mean ± SD.