The
prenyl diphosphate synthase subunit 2 (PDSS2) gene has recently been proposed as a novel
tumor suppressor in several types of solid
tumors. However, the mechanism of its
tumor-suppressing activity is not known. Our previous study found a decreased expression of PDSS2 in clinical samples of
non-small-cell lung cancer, and an inverse correlation between PDSS2 levels and stages of
tumor differentiation and
lymph node metastasis. In this study, we further investigated the
tumor-suppressing activity of PDSS2 in
lung cancer cells using cellular and molecular tools. The PDSS2 gene has low levels of expression in human
lung cancer cell lines. We transfected and overexpressed PDSS2 in the NCI-H1299
lung cancer cell line. The forced overexpression caused massive cell death (~70%) through apoptotic pathways and significantly inhibited colony formation. At the same time, repression of PDSS2 expression by
siRNA enhanced the growth of a noncancerous lung epithelial cell line MRC-5. There was an inverse correlation (Pearson's test, r=-0.9373) between PDSS2 expression and
gelsolin expression, which is known to inhibit apoptosis and enhance cell invasion and
metastasis. The ability of PDSS2 to repress
gelsolin might contribute to its
tumor-suppressing activity. However, PDSS2 did not influence the sensitivity of the
lung cancer cells to chemotherapeutic drugs. Taken together, PDSS2 has
tumor-suppressing activity in human
lung cancer cells by enhancing apoptosis and inhibiting tumorigenic capacity.