Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β-catenin signaling

Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25（OH）2D] are mediated through binding to the vitamin D receptor （VDR）. Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad （MDA-MB-231）, subcutaneously （PC3） or intra-tibially （both cell lines） in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/0-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 （IL-6）, and IL-8. Stabilization of 0-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.

Electromagnetically Induced Transparency in a Cold Gas with Strong Atomic Interactions

Electromagnetically induced transparency （EIT） is investigated in a system of cold, interacting cesium Rydberg atoms. The utilized cesium levels 6S1/2, 6P3/2 and nD5/2 constitute a cascade three-level system, in which a coupling laser drives the Rydberg transition, and a probe laser detects the EIT signal on the 6S1/2 to 6/23/2 transition. Rydberg EIT spectra are found to depend on the strong interaction between the Rydberg atoms. Diminished EIT transparency is obtained when the Rabi frequency of the probe laser is increased, whereas the corresponding linewidth remains unchanged. To model the system with a three-level Linclblad equation, we introduce a Rydberg-level dephasing rate γ3 = κ×（P33/Ωp）^2, with a value κ that depends on the ground-state atom density and the Rydberg level, The simulation results are largely consistent with the measurements. The experiments, in which the principal quantum number is varied between 30 and 43, demonstrate that the EIT reduction observed at large Ωp is due to the strong interactions between the Rydberg atoms.