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.Mutations in the parkin gene, located on chromosome 6q25.2-27, are a predominant cause of inherited parkinsonism (1). Accordingly, much of the interest in characterizing the function of the parkin gene has been directed toward understanding its role in neurodegeneration. However, aberrant parkin function has also been linked to several other disorders (2, 3), among which, to the development of several types of cancers (4). Comparatively, the role of parkin in these disorders is less well characterized.Supporting a role for parkin in cancers, a previous study by Cesari et al. (4) involving physical mapping combined with loss of heterozygosity (LOH) 4 analysis identified the 6q-located, 1.4 Mb parkin as a gene that is frequently targeted by hemizygous deletion and inactivation in both malignant tumors and tumorderived cell lines. Following this discovery, several other groups have reported parkin gene alterations and expression variability in a variety of tumor biopsies and tumor cell lines representing a wide range of cancers including breast and ovarian cancers (4 -8). Frequently, diminished or absent parkin expression was observed in these cancers, suggesting that parkin may have tumor suppression properties. Consistent with this, microcellmediated transfer of human chromosome 6 suppresses tumorigenicity in several cancer cell lines (9), and introduction of an intact chromosome 6 into MCF7 (a breast cancer cell line) restores its ability to senesce (10). Collectively, these studies support the existence of a tumor suppressor gene (TSG) on chromosome 6q and the potential candidacy of parkin as a TSG. However, whether and how the loss of parkin function contributes to the development of cancers are currently not well...

Scorpions and their venoms have been used in traditional medicine for thousands of years in China, India and Africa. The scorpion venom is a highly complex mixture of salts, nucleotides, biogenic amines, enzymes, mucoproteins, as well as peptides and proteins (e.g. neurotoxins). One of the recently observed biological properties of animal venoms and toxins is that they possess anticancer potential. An increasing number of studies have shown that scorpion venoms and toxins can decrease cancer growth, induce apoptosis and inhibit cancer progression and metastasis in vitro and in vivo. Several active molecules with anticancer activities, ranging from inhibition of proliferation and cell cycle arrest to induction of apoptosis and decreasing cell migration and invasion, have been isolated from scorpion venoms. These observations have shed light on the application of scorpion venoms and toxins as potential novel cancer therapeutics. This mini-review focuses on the anticancer potential of scorpion venoms and toxins and the possible mechanisms for their antitumor activities.

Depending on the amounts present, reactive oxygen species can exert either beneficial or deleterious effect to cells. In the present study, we observed a decrease in cell viability concomitant with an increase of malondialdehyde concentration in hydrogen peroxide (H(2)O(2))-treated MCF-7 breast cancer cells. There was also a concurrent G1/S phase cell cycle arrest with increased apoptosis in H(2)O(2)-treated cells. Analysis of 84 oxidative stress related genes showed that five genes were significantly and differentially regulated, namely, Cytoglobin (CYGB), Forkhead box M1 (FOXM1), NADPH oxidase (NOX5), Nudix (nucleoside diphosphate linked moiety X)-type motif 1 (NUDT1) and Selenoprotein P1 (SEPP1) genes with H(2)O(2) treatment. It would seem that oxidative stress induces cell cycle arrest in the breast cancer by modulation of these genes. Manipulation of these genes, in particular FOXM1, a proliferation-specific gene associated with human malignancies, could stifle cancer progression and enhance the therapeutic efficacy of drugs which exert their effects by oxidative stress.

Cell surface receptors play an important role in mediating cell communication and are used as disease biomarkers and therapeutic targets. We present a one-pot molecular toolbox, which we term the split proximity circuit (SPC), for the autonomous detection and visualization of cell surface receptor clusters. Detection was powered by antibody recognition and a series of autonomous DNA hybridization to achieve localized, enzyme-free signal amplification. The system under study was the human epidermal growth factor receptor (HER) family, that is, HER2:HER2 homodimer and HER2:HER3 heterodimer, both in cell lysate and in situ on fixed whole cells. The detection and imaging of receptors were carried out using standard microplate scans and confocal microscopy, respectively. The circuit operated specifically with minimal leakages and successfully captured the receptor expression profiles on three cell types without any intermediate washing steps.

Serglycin is a multifunctional molecule and one of the first proteoglycans to be cloned. In this manuscript, we examine the physiological roles of serglycin in immunity, hemostasis, cell growth, apoptosis, and reproduction. In addition, we review recent studies on the involvement of serglycin in various pathological conditions, including cancer, inflammatory diseases, and platelet disorders. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.

Gastric carcinoma arises from aberrant growth of normal gastric mucosa. There is increasing evidence that claudins (CLDNs) may play a critical role in the significant steps of gastric tumorigenesis, from metaplasia to metastasis. The CLDN family which consists of at least 27 member proteins is known to mediate selective permeability in cellular tight junctions. It is now established that CLDNs are differentially altered in gastric cancer and CLDN proteins are believed to play different roles in the growth and progression of gastric cancer.

Peroxiredoxin I to VI (PRX I-VI), a family of highly conserved antioxidants, has been implicated in numerous diseases. There have been reports that PRXs are expressed aberrantly in a variety of tumors, implying that they could play an important role in carcinogenesis. Epigenetic mechanisms such as DNA methylation, histone modifications, and microRNAs have been reported to modulate expression of PRXs. In addition, the use of epigenetic regulators, such as histone deacetylases, has been demonstrated to restore PRX to normal levels, indicating that the reversible nature of epigenetics can be exploited for future treatments.

Abstract. Peroxiredoxin III (Prx III), an antioxidant protein found in mitochondria, plays an essential role in mitochondrial homeostasis. Aberrant expression of Prx III has been implicated in the tumorigenesis of various cancers. In this study, we evaluated the expression of Prx III in breast cancer tissues and elucidated its role in cell proliferation, a hallmark of cancer. Breast tissue microarrays comprising 106 breast cancer sections were stained with Prx III antibody using immunohistochemisty and correlated with proliferating cell nuclear antigen (PCNA) immunostaining. To validate the role of Prx III in cell proliferation, expression of Prx III was analyzed at the mRNA and protein levels by real-time RT-PCR, Western blotting and immunofluorescence in vitro. siRNA mediated silencing of Prx III in MDA-MB-231 breast cancer cells was performed and the effect on the cell cycle was examined. Prx III expression in patient tissue microarray samples was found to be positively associated with PCNA immunostaining, a proliferative marker. Prx III was expressed in both MCF-7 and MDA-MB-231 breast cancer cell lines and transient transfection with siPrx III in MDA-MB-231 cells induced inhibition of cell proliferation and cell cycle arrest. The data suggests that Prx III has a significant role in cell cycle regulation and could be a potential proliferation marker in breast cancer.