eEF1A2 (eukaryotic protein elongation factor 1 alpha 2) is a protein translation factor that is likely a human oncogene by virtue of its capacity to transform mammalian cells and its high expression in tumors of the ovary, breast and lung. Here, we show that expression of eEF1A2 is sufficient to stimulate the formation of filopodia in BT549 human breast cancer cells and non-transformed Rat2 cells. Filopodia formation in eEF1A2-expressing cells is dependent on the activity of phosphatidylinositol-3 kinase (PI3K), and the ROCK and Akt kinases. Furthermore, eEF1A2 expression is sufficient to activate Akt in a PI3K-dependent fashion and inactivation of eEF1A2 by short interfering RNA reduces Akt activity. Using breast cancer cell line BT 549, we show that eEF1A2 expression stimulates cell migration and invasion in a largely PI3K-and Akt-dependent manner. These results suggest that eEF1A2 regulates oncogenesis through Akt and PI3K-dependent cytoskeletal remodeling.
Breast cancer is the most common malignancy among North American women. The identification of factors that predict outcome is key to individualized disease management and to our understanding of breast oncogenesis. We have analyzed mRNA expression of protein elongation factor eEF1A2 in two independent breast tumor populations of size n = 345 and n = 88, respectively. We find that eEF1A2 mRNA is expressed at a low level in normal breast epithelium but is detectably expressed in approximately 50-60% of primary human breast tumors. We have derived an eEF1A2-specific antibody and measured eEF1A2 protein expression in a sample of 438 primary breast tumors annotated with 20-year survival data. We find that high levels of eEF1A2 protein are detected in 60% of primary breast tumors independent of HER-2 protein expression, tumor size, lymph node status, and estrogen receptor (ER) expression. Importantly, we find that high eEF1A2 is a significant predictor of outcome. Women whose tumor has high eEF1A2 protein expression have an increased probability of 20-year survival compared to those women whose tumor does not express substantial eEF1A2. In addition, eEF1A2 protein expression predicts increased survival probability in those breast cancer patients whose tumor is HER-2 negative or who have lymph node involvement.
Healthy women at reproductive age experience a cyclical alteration of gastrointestinal (GI) symptomatology during their menstrual cycle. Additionally, the majority of healthy women also complain of worsening of GI symptoms either during the premenstrual or menstrual phase. Despite conflicting evidence, studies suggest that sex hormones may increase GI transit time during the luteal phase. Similar phenomenon is also observed in women with underlying inflammatory bowel disease (IBD). The mechanism underlying this complex pathophysiology is still not completely understood. However, a possible influence of sex hormones on the brain-gut-microbiota axis is hypothesized. The diagnosis of IBD is associated with a delay in menarche as well as menstrual function irregularities including alterations in cycle length and the duration of flow. There is little data on the effect of menopause on IBD disease activity and conflicting data on the effect of IBD diagnosis on the onset of menopause. The role of contraceptives and hormone replacement therapies on the development or disease activity of IBD has not been yet established. Moreover, IBD patients with concomitant dysmenorrhea report heightened pain during menses. The effect of non-steroidal anti-inflammatory drugs in treating primary dysmenorrhea on the disease course of IBD is unknown. In addition, the effect of IBD medications including immunomodulators and biologics on menstrual function remains unclear. Also, the role of IBD surgery on menstrual irregularities needs to be fully elucidated. Hence, understanding the influence of menstrual function on IBD disease activity and vice versa and the maintenance of normal menstrual function in those patients is important in improving overall reproductive health and fertility and outcome of IBD.
RESULTS: Inflammatory bowel disease (IBD) is a chronic inflammatory condition with a waxing and waning clinical course. Several studies have reported a similar rate of flare between pregnant and non-pregnant patients, estimated to be between 26% and 34%. Steroid therapy is an essential part of treatment. Some studies have shown steroid-resistant disease in 15% of ulcerative colitis patients and 20% in Crohn's disease with the prevalence of CMV infection between 21% and 36%. The clinical significance of CMV infection in inflammatory bowel disease has been a matter of debate with some studies suggesting that CMV is a bystander in severe disease, especially in the immunosuppressed, while others correlate flares with CMV disease. There are no large randomized controlled trials discussing the impact of CMV therapy in patients with IBD flares. Further, there is scant data on how to treat CMV colitis in pregnant patients. CONCLUSIONS: Diagnosis of CMV colitis must be considered in patients with severe colitis flare not responding to steroid therapy. This is imperative before initiation of immunosuppressive therapies. Timely diagnosis and treatment of CMV colitis helped attain remission and avoid complications of disease flare in our pregnant patient in third trimester of her pregnancy. P-017 YI
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