Differential expression of survivin-2B and survivin-ΔEx3 is inversely associated with disease relapse and patient survival in non-small-cell lung cancer (NSCLC)

Although it was observed that inhibition of the antiapoptotic protein survivin expression in lung cancer cells induces apoptosis, the expression and role of survivin variants (survivin-2B and survivin-Delta Ex3) in lung cancer have not yet been characterized. We analyzed 24 non-small-cell lung cancer (NSCLC) samples by semi quantitative RT-PCR. Surprisingly, our results revealed that high-level expression of survivin-2B is significantly associated with the patient category of "no relapse and alive" (p-value < 0.0001). In contrast, high-level expression of survivin-Delta Ex3 is highly associated with the patient category of "relapse and dead" (p-value < 0.0001). Consistent with this observation, exogenous expression of survivin-2B in A549 lung cancer cells inhibited cell growth, disrupted the mitochondria potential, and induced apoptotic cell death, while expression of survivin-Delta Ex3 protected the mitochondria potential and facilitated cell survival. These findings provide evidence that survivin-2B and survivin-Delta Ex3 play opposite roles in disease relapse and NSCLC cell survival, which is likely through the differential modulation of mitochondrial potential. Thus, controlling the differential expression of survivin-2B and survivin-Delta Ex3 may represent novel approaches for cancer therapeutics in NSCLC. (c) 2005 Elsevier Ireland Ltd. All rights reserved.