KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients
(2016)
Numerous studies showed abnormal expression of ion channels in different cancer types. Amongst these, the potassium channel gene KCNJ3 (encoding for GIRK1 proteins) has been reported to be upregulated in tumors of patients with breast cancer and to correlate with positive lymph node status. We aimed to study KCNJ3 levels in different breast cancer subtypes using gene expression data from the TCGA, to validate our findings using RNA in situ hybridization in a validation cohort (GEO ID GSE17705), and to study the prognostic value of KCNJ3using survival analysis. In a total of > 1000 breast cancer patients of two independent data sets we showed a) that KCNJ3 expression is upregulated in tumor tissue compared to corresponding normal tissue (p < 0.001), b) that KCNJ3 expression is associated with estrogen receptor (ER) positive tumors (p < 0.001), but that KCNJ3 expression is variable within this group, and c) that ER positive patients with high KCNJ3 levels have worse overall (p < 0.05) and disease free survival probabilities (p < 0.01), whereby KCNJ3 is an independent prognostic factor (p <0.05). In conclusion, our data suggest that patients with ER positive breast cancer might be stratified into high risk and low risk groups based on the KCNJ3 levels in the tumor.
Mechanical interaction between cells - specifically distortion of tensional homeostasis-emerged as an important aspect of breast cancer genesis and progression. We investigated the biophysical characteristics of mechanosensitive ion channels (MSCs) in the malignant MCF-7 breast cancer cell line. MSCs turned out to be the most abundant ion channel species and could be activated by negative pressure at the outer side of the cell membrane in a saturable manner. Assessing single channel conductance (GΛ) for different monovalent cations revealed an increase in the succession: Li⁺ < Na⁺ < K⁺ ≈Rb⁺ ≈ Cs⁺. Divalent cations permeated also with the order: Ca²⁺ < Ba²⁺. Comparison of biophysical properties enabled us to identify MSCs in MCF-7 as ion channels formed by the Piezo1 protein. Using patch clamp technique no functional MSCs were observed in the benign MCF-10A mammary epithelial cell line. Blocking of MSCs by GsMTx-4 resulted in decreased motility of MCF-7, but not of MCF-10A cells, underscoring a possible role of Piezo1 in invasion and metastatic propagation. The role of Piezo1 in biology and progression of breast cancer is further substantiated by markedly reduced overall survival in patients with increased Piezo1 mRNA levels in the primary tumor.
The arrival of high-mobility two-dimensional materials like graphene leads to the renaissance of former vertical semiconductor–metal–semiconductor (SMS) hot electron transistors. Because of the monolayer thickness of graphene, improved SMS transistors with a semimetallic graphene-base electrode are now feasible for high-frequency applications. In this study we report about a device that consists of amorphous silicon, graphene, and crystalline silicon. For the first time, this device is fabricated by a four-mask lithography process which leads to significant improvements in the device performance. A strongly increased common-emitter current gain of 2% could be achieved while the on–off ratio improved to 1.6 × 105, which is already higher than predicted theoretically. This could be mainly attributed to better interface characteristics and decreased lateral dimensions of the devices. A cutoff frequency of approximately 26 MHz could be forecasted based on the DC measurements of the device.
A graphene-based three terminal barristor device was proposed to overcome the low on/off ratios and insufficient current saturation of conventional graphene field effect transistors. In this study, we fabricated and analyzed a novel graphene-based transistor, which resembles the structure of the barristor but uses a different operating condition. This new device, termed graphene adjustable-barriers transistor (GABT), utilizes a semiconductor-based gate rather than a metal−insulator gate structure to modulate the device currents. The key feature of the device is the two graphene-semiconductor Schottky barriers with different heights that are controlled simultaneously by the gate voltage. Due to the asymmetry of the barriers, the drain current exceeds the gate current by several orders of magnitude. Thus, the GABT can be considered an amplifier with an alterable current gain. In this work, a silicon−graphene−germanium GABT with an ultra-high current gain (ID/IG up to 8 × 106) was fabricated, and the device functionality was demonstrated. Additionally, a capacitance model is applied to predict the theoretical device performance resulting in an on−off ratio above 106, a swing of 87 mV/dec, and a drivecurrent of about 1 × 106 A/cm2.