Causes And Effects Of Limk1

An abnormality in this process leads to a number of problems, including cancer. MicroRNAs are a type of RNA which inhibit the expression of genes and play a vital role in the development of cancer. Of notable interest is miR-378, as it increases tumor angiogenesis and growth and also enhances the survival of these cells, by decreasing the expression of tumor suppression genes like Sufu. A study testing human cell lines found that when Sufu expression levels were high, miR-378 expression levels were low, and when Sufu levels were low, miR-378 levels were high, showcasing that the two were negatively correlated. Because repression of Sufu can lead to rampant proliferation of cells, the inhibition of Sufu is essential in order for miR-378 to promote angiogenesis and increase cell

By secreting this protein, VEGF receptors in the vasculature then activate the extracellular kinase and mitogen-activated protein (MAP) kinase signal transduction pathway. This induces proteins that breakdown the blood vessels basement membrane, allowing endothelial cells to invade. The breakdown of the membrane allows fluid and proteins to escape through the vasculature. One of these proteins, matrix metalloproteinase (MMP), breaks down the extracellular matrix between the tumour and blood vessel and allows the VEGF to stimulate receptors on the new endothelial cells. This causes proliferation of the endothelial cells, tube formation and migration towards the area signalling VEGF (the tumour cells), allowing the growth of new blood vessels into the tumour. (Spyridopoulos, I. 2002).

Breast cancer is a complex and heterogeneous disease caused by both genetic and non-genetic risk factors. These factors include, mutations in breast cancer-associated genes 1 and 2 (BRCA1 and BRCA2) [1]; loss or aberrant expression of the estrogen receptor (ER) [2]; human epidermal growth factor receptor (HER2) overexpression [3] ; lack of ER, progesterone receptor (PR), and epidermal growth factor receptor (EGFR) expression[4] ; high levels of receptor for the insulin-like growth factor receptor 1 (IGF-1R[5]; and expression of microRNA (miRNA) [6]. In addition to genetic alterations (gene amplifications, deletions, point mutations, and chromosome rearrangements), epigenetic changes (methylation and/or acetylation) of the genome play an important role in breast carcinogenesis. For example, methylation of RASSF1A, BRCA1, and estrogen receptor α (ERα) is associated with breast tumorigenesis and metastasis [7]. The inactivation of tumor suppressor proteins that lead to tumor cell growth and survival are another mechanism of breast cancer development [8]. These genes are inactivated by a variety of mechanisms, including chromosomal deletions, intragenic mutations, proteolysis, and loss of epigenetic modifications [9]. The best-characterized tumor suppressor protein is p53. In breast cancer, p53 mutation or downregulation is associated with an adverse prognosis [10]. Other tumor suppressor proteins in breast cancer include PTEN [11], p16[12], the retinoblastoma gene[13], and

Breast cancer exists today as a vicious disease which has multiple facets for killing its host. The largest indicator of survival rate is length of time alive after diagnosis with the disease, and then whether or not the disease has metastasized to a new location in the body. For breast cancer patients, the 5-year survival rate of patients below Stage 4 is 90%. The stages below the 4 stage represent the stages where the breast cancer has not metastasized into other regions of the body. When breast cancer metastasizes into another region of the body, the 5-year survival rate of these individuals drops to 22%. The most common places of metastasis include the brain, liver, and lungs. The goal of studying cell line 231BR is that of

As medicine is growing in our times, researcher are looking for a new medicine to fight female breast cancer. Many people talk about the topic of breast cancer, but do they truly know what it is? In which case, I would be happy to inform you about breast cancer. Breast cancer is a disease in which tissue cells from the breast starts growing in an abnormal and uncontrollable way. These cells usually form a malignant tumor inside the breast and it is often felt as a lump or seen in an mammogram. There are different types of cancer such as: ductal carcinoma, lobular carcinoma, and inflammatory breast cancer. Researchers are looking for new ways that might lower the risk of obtaining breast cancer especially in cases where it is hereditary.

In women worldwide, more than 1 million women were diagnosed in 2012, making the breast cancer the most commun cancer (1). In United States, breast cancer represent 29% of new cases expected to be diagnosed in 2015 of all cancer, and is one of the most common cancer diagnosed after skin cancer. It is also unfortunatley the second cause of death cancer within women, and 17% death cases are expected in 2015 for invasive breast cancer (IBC), among the new cases (2). Among the 61% of the breast cancer diagnosed at a confined stage, the 5-year survival rate is up to 99%, whereas it can drops to 25% when metastasis can be seen at time of diagnosis(2). The early detection of breast cancer is made by a clinical breast exam and a mammography for most of women, and has shown to reduce mortality since many years (3) with an incidence rate staying stable among women, which is the results of improvement of technics of detection for early diagnosis and treatement (2).

Cancer metastasis in the main character and hallmark of cancer progression [6]. Metastasis is a multi-step process beginning from detachments of cancer cells from the primary tumor, disruption of the basement membrane for invading to surrounding tissue. Subsequently, the cancer cells able entry to the blood and lymphatic system to spread into other part of the body and extravasation for growth and proliferate in distant sites [7]. Matrix metalloproteinase (MMP) is a zinc-dependent endopeptidase which responsible in degradation the component of extracellular matrix (ECM) proteins including collagen, elastin, fibronectin. MMP can secrete by inflammatory cells, osteoblast, fibroblast, and also cancer cells. MMP has a pivotal role in promoting

Importantly, the ERM protein ezrin itself is a well-known mediator of metastasis (Elliott et al., 2005; Khanna et al., 2004; Meng et al., 2010). Many clinical studies have linked high expression of ezrin with poor outcome in cancer patients suffering from a wide variety of cancers, including prostate, breast can lung cancer (Clucas and Valderrama, 2014). Interestingly, specifically the abnormal distribution of ezrin in breast cancer patients, from the apical regions of non-tumorigenic cells to motile projections in invasive cells, has been correlated with poor prognosis (Sarrio et al., 2006). In addition, it has previously been indicated as an important regulator of metastasis in the murine carcinoma cell line AC2M2 (Elliott et al., 2005). Furthermore, ezrin overexpression has been shown in various studies to promote the survival, migration and/or invasion of cancer cells into surrounding tissue and to disrupt cell-cell contacts (Clucas and Valderrama, 2014).

MicroRNAs are a class of small (17–25 nucleotides) single-stranded noncoding RNAs that function as a sequence-targeted modifiers of gene expression through translational repression [4]. The miRNAs are important key regulators of normal hematopoiesis and their disruption could lead to leukemogenesis [5]. Mutations like single-nucleotide polymorphisms located in microRNA binding sites can cause disruption in microRNA-target interactions, leading to deregulation of the target gene expression [6].

We have therefore further characterized the functional roles of IL-6 in the metastasis of breast cancer and demonstrated that IL-6 is a promising molecular target for the development of molecularly-targeted therapeutic strategies against IL-6. In this study, to characterize the extent to which IL-6 is capable of inducing a metastatic phenotype, we established IL-6 over-expression cell lines MCF-7IL-6 2# and MCF-7IL-6 14# and IL-6 knockdown cell lines MDA-MB-231/IL-6-/+. We employed the breast cancer model in conjunction with gene expression profiling with RNA-seq data as an efficient tool for high-throughput analysis and to screen for differentially expressed genes. Our aim was to identify the gene candidates essential for IL-6-promoted tumor metastasis and invasion by comparing IL-6 over-expression cell lines MCF-7IL-6 2# and MCF-7IL-6 14# with MCF-7, IL-6 knockdown cell lines MDA-MB-231/IL-6-/+ with MDA-MB-231. We found that IL-6 significantly promoted breast cancer metastasis in vivo and in vitro. Furthermore, we also suggested a novel role for the CDKN1A and EPAS1 as a crucial factor in the IL-6-induced migration and invasion of breast

Silva et al. (Ref. 83) have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% overexpression and 26% decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression showed one or more of these genetic alterations (Ref. 83). A significant correlation was observed between decreased p14ARF expression and poor prognostic parameters. The same group later studied the inactivation mechanisms that alter the levels (Ref. 84). Furthermore, the interdependence of inactivation mechanisms was studied since it had been reported that p14ARF was altered in tumors in concordance with p16INK4a. They showed that promoter hypermethylation was the major mechanism of inactivation of these genes, which was present in 31% and 50% of the tumors that showed decreased p16INK4a and p14ARF expression, respectively. No detectable inactivation mechanisms were observed in tumors overexpressing p16INK4a or p14ARF. In conclusion, these tumor suppressor proteins were often co-altered in human breast

Regarding MMP-3 immunostaining results, no significant difference was detected between the MMP-3 polymorphism genotypes and the strength of anti MMP-3 immunostaining in controls and patient tissue samples and even among different disease stages. Our results were in accordance with studies of Nishioka et al.(2000) in endometrial carcinoma, Xuan et al in breast cancer, and with Zinzindohoué et al.(2005) in colorectal cancer who suggested the importance of MMP-1-1607ins/del G functional polymorphism in regulating the transcription level of MMP-1 . Moreover they have suggested a relationship between MMP-1 expression and each of cancer invasion, metastasis, and prognosis. In contrary to our results Beeghly –Fadiel et al.(2008), Hettiaratchi et al.(2007), and Guan et al.(2014) have reported a nonsignificant association of MMP-1 promoter polymorphism and significant association of the

Breast cancers mostly invade into adjacent regions and metastasize to lymph nodes and distant organs. To develop novel treatments strategies, it is essential to address factors underlying tumorgenesis, invasion and metastasis. In this study, we identified Bmi-1, S100A4 and claudin-1 as important players in breast cancer progression. The current study illustrated the expression of these markers in primary breast cancer tissues, followed by demonstrating the association between their expressions and clinicopathological features and finally addressed their role in breast cancer prognosis.

MicroRNAs (miRNAs) comprise a large family, its having approximately 20–22 nucleotides, and it regulates the expression of target genes at the post-transcriptional level. However, thousands of miRNAs have been identified in many organisms (roundworms, flies, fish, frogs, mammals, flowering plants, mosses, and even viruses) by using genetics, molecular cloning and predictions from bioinformatics technique (Lagos et al., 2001; Lim et al., 2003; Pfeffer et al., 2004; Axtell and Bartel, 2005). The whole human genome encodes at least 474 miRNA genes (Griffiths, 2004; Griffiths et al., 2006), and in human breast cancer there are 133 miRNAs were identified. MiRNAs control messenger RNA expression and which are frequently dysregulated in

During tumour progression, angiogenesis is constantly being induced leading to the formation of vasculature from otherwise quiescent endothelial cells (5,15,16). Tumour induced angiogenesis leads to the production of aberrant, distorted and leaky vasculature (16) which promote tumour growth by increasing the blood supply in targeted areas. A study observed that cancer cells expressing the oncoproteins Bcl-2 or Bcl-xl had a less proliferative and less angiogenic effect when compared to the parental cancer cells which lacked the apoptotic inhibiting proteins and where more proliferative (13), linking angiogenesis promotion with more proliferative cancers. There are a number of matrix/non-matrix derived inhibitors and promoters of angiogenesis which control the stimulation or inhibition of angiogenesis. It has been shown that overexpression of certain endogenous inhibitors suppresses angiogenesis and limiting tumour growth. In certain cases, not only is angiogenesis effected but carcinoma cell migration is decreased showing a direct anti-tumour effect (27).