Parkin Enhances the Expression of Cyclin-dependent Kinase 6 and Negatively Regulates the Proliferation of Breast Cancer Cells*

Although mutations in the parkin gene are frequently associated with familial Parkinsonism, emerging evidence suggests that parkin also plays a role in cancers as a putative tumor suppressor. Supporting this, we show here that parkin expression is dramatically reduced in several breast cancer-derived cell lines as well as in primary breast cancer tissues. Importantly, we found that ectopic parkin expression in parkin-deficient breast cancer cells mitigates their proliferation rate both in vitro and in vivo, as well as reduces the capacity of these cells to migrate. Cell cycle analysis revealed the arrestment of a significant percentage of parkin-expressing breast cancer cells at the G1-phase. However, we did not observe significant changes in the levels of the G1-associated cyclin D1 and E. On the other hand, the level of cyclin-dependent kinase 6 (CDK6) is dramatically and selectively elevated in parkin-expressing breast cancer cells, the extent of which correlates well with the expression of parkin. Interestingly, a recent study demonstrated that CDK6 restrains the proliferation of breast cancer cells. Taken together, our results support a negative role for parkin in tumorigenesis and provide a potential mechanism by which parkin exerts its suppressing effects on breast cancer cell proliferation

Equilibrium Trip Scheduling in Congested Traffic under Uncertainty

Whilst traditional modeling and research efforts put emphasis on the effect of congestion on travel choices, recently more and more studies examine the notion of travel time uncertainty on travel decision. In particular, travel time reliability forms an important component in modeling route choice and trip scheduling. This paper considers equilibrium trip scheduling under random travel delay in a single bottleneck. Travelers form a heterogeneous population with distinctive requirements on the probability of punctual arrival and each with a different valuation toward earliness and lateness. The analysis shows that random delay plays a significant role in travel costs and introduces substantial differences in the queuing pattern, departure and arrival times, as compared with the traditional deterministic model