Combined genomic and phenotype screening reveals secretory factor SPINK1 as an invasion and survival factor associated with patient prognosis in breast cancer.
Bottom Line: In ER- cases, the prognostic effect did not reach statistical significance.However, down-regulation of SPINK1 resulted in cell death.Intriguingly, these anti-apoptotic effects of SPINK1 were abrogated by mutations of its protease inhibition domain.
Affiliation: Cancer Biology and Pharmacology, Genome Institute of Singapore.Show MeSH
Related in: MedlinePlus
Mentions: To test if the in vitro invasiveness of MDA-MB-231 cells was similarly affected in vivo, we injected MDA-MB-231 cells over-expressing SPINK1 (MB231 SPINK1OE) into the tail-vein of Balb/c nu/nu mice. Figure 11 shows that SPINK1 expression led to increase in both the number and size of metastatic lesions in the mouse lung. Mice injected with MB231-vector cells had only 4.1% ± 2.7 lesions larger than 200 µm, while MB231 SPINK1OE cells gave rise to significantly larger lesions with 24.8% ± 8.5 larger than 200 µm (p < 0.05). The MB231 SPINK1OE cells also formed almost threefold more lesions than that of the control cells (p < 0.05). In concordance with our in vitro data, MCF-7 SPINKOE cells did not show lung metastases in vivo (data not shown). These data suggest that in breast tumour cells with prior capacity to invade, high SPINK1 expression may lead to increased metastasis as compared to the same cells expressing relatively lower amounts. However, due to unavailability of a suitable invasive model system, SPINK1 effects in ER+ cells remain unexplored.
Affiliation: Cancer Biology and Pharmacology, Genome Institute of Singapore.