Figure 4

The endogenous mevalonate pathway mediates the maturation of aberrant Ras signals in PCa devoid of the mitochondrial genome. (a) Confocal images (z-slices) of anti-total-Ras (Alexa-488 labeled-anti-mouse IgG) within an intracellular plane of formaldehyde fixed cultures of the indicated cell lines. Matched image sets were mapped to a common linear gray-scale range (^*overexposed image of LNCaP). Scale bars represent 20 μm. (b) Confocal images (z-slices) of anti-total-Ras in mtDNA-KO (LNρ0-8) cells cultured 12 h in the absence (control) or presence of lovastatin (5 μM) with or without mevalonate (1 mM). (c and d) Phospho-ERK, total ERK, phospho-Akt, total AKT and β-actin in total-protein lysates (30 μg) of LNρ0-8 cells cultured 24 h in the absence (control) or presence of lovastatin (c), or (d) 48 h in the absence (control) or presence of FTI-276. (e) HMGR in total-protein lysates (30 μg) of the parental, mtDNA-KO and mtDNA-KI of LNCaP. (f) HMGR in total-protein lysates (30 μg) of indicated cells as assessed by western blot with anti-HMGR