Project description:To identify differentially regulated genes between wild-type and Pak1 deficient mouse breast cancer cells, we performed a comparative gene profiling study by using mouse whole genome arrays.
Project description:To identify differentially regulated genes between wild-type and Pak1 deficient mouse breast cancer cells, we performed a comparative gene profiling study by using mouse whole genome arrays. We compared the gene expression profiles of Her2 positive : Pak1 deficient cells vs Her2 positive : Pak1 wild type cells. All the experiments were performed in duplicate using tumor derived cells from two different tumors per group.
Project description:To identify differentially regulated genes between wild-type and Pak1 deficient human breast cancer cells, we performed a comparative gene profiling study by using human whole genome arrays.
Project description:To identify differentially regulated genes between wild-type and Pak1 deficient human breast cancer cells, we performed a comparative gene profiling study by using human whole genome arrays. We compared the gene expression profiles of MCF10A.B2 cells (MCF10A cells expressing a chemically activatable form of Her2) stably expressing a Tet inducible shRNA directed against Pak1 gene. All the experiments were performed in duplicate using tumor derived cells from two different tumors per group.
Project description:To identify differentially phosphorylated proteins between wild-type and Pak1-deficient mouse breast cancer cells, we performed a comparative study by using phospho-antibody arrays.
Project description:Background Adjuvant tamoxifen therapy approximately halves the risk of estrogen receptor-positive (ER+) breast cancer recurrence, but many women do not respond to therapy. Observational studies nested in clinical trial populations suggest that overexpression or nuclear localization of p21-activated kinase 1 (Pak1) in primary tumors predicts tamoxifen failure. Material and methods We measured the association between Pak1 expression and breast cancer recurrence in a Danish population-based case-control study. Pak1 cytoplasmic expression level and nuclear positivity were determined by immunohistochemical staining of primary breast tumors from recurrence cases and matched controls from two breast cancer populations; women diagnosed with ER-positive tumors who received at least one year of tamoxifen therapy (ER+/TAM+), and women diagnosed with ER-negative tumors who survived for at least one year (ER-/TAM-). Pak1 staining was assessed by a single, blinded pathologist, and associations were estimated with conditional logistic regression models. Results We included 541 recurrence cases and 1:1 matched controls from the ER+/TAM + group and 300 recurrence cases and 1:1 matched controls from the ER-/TAM - group. Pak1 cytoplasmic intensity was not associated with breast cancer recurrence in either group (ER+/TAM + ORadj for strong vs. no cytoplasmic staining = 0.91, 95% CI 0.57, 1.5; ER-/TAM - ORadj for strong vs. no cytoplasmic staining = 0.74, 95% CI 0.39, 1.4). Associations between Pak1 nuclear positivity and breast cancer recurrence were similarly near null in both groups. Conclusion Pak1 positivity in primary breast tumors was neither predictive nor prognostic in this prospective, population-based study.
Project description:MicroRNA (miRNA) is involved in the progression and metastasis of diverse human cancers, including breast cancer, as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. Here, we show that miR-494 is decreased in human breast cancer specimens and breast cancer cell lines. Ectopic expression of miR-494 in basal-like breast cancer cell lines MDA-MB-231-LUC-D2H3LN and BT-549 inhibits clonogenic ability and metastasis-relevant traits in vitro. Moreover, ectopic expression of miR-494 suppresses neoplasm initiation as well as pulmonary metastasis in vivo. Further studies have identified PAK1, as a direct target gene of miR-494, contributes to the functions of miR-494. Remarkably, the expression of PAK1 is inversely correlated with the level of miR-494 in human breast cancer samples. Furthermore, re-expression of PAK1 partially reverses miR-494-mediated proliferative and clonogenic inhibition as well as migration and invasion suppression in breast cancer cells. Taken together, these findings highlight an important role for miR-494 in the regulation of progression and metastatic potential of breast cancer and suggest a potential application of miR-494 in breast cancer treatment.
Project description:IntroductionThe prognosis of breast cancer depends on several clinical and pathological parameters most importantly the clinical stage, other factors predicting the outcome are hormone receptors like estrogen and progesterone receptors. Expression of Ki67 also have been shown to affect the outcome.Patients and methodsThis retrospective study included 278 female patients diagnosed and operated for breast cancer. Patients were grouped into 2 groups according to the expression of Ki67 to those with positive and those with negative expression. Both groups were compared for differences.ResultsThe mean age was 48.61 years and the right breast was the commonest affected side, the mean tumor size was 34 mm, 70% had axillary LN involvement, 50% had intermediate tumor grade, and 85.6% had no recurrence. Most patients had stage IIA, IIB, and IIIA, 67.6% had positive expression of Ki67 and had a significant correlation with the tumor grade, tumor necrosis, and ER expression (P values 0.001, 0.047, and 0.002) respectively, while the correlation was negative with recurrence, axillary LN involvement, TNM stage, site of the tumor, age, tumor size, PR and HER-2 receptor (P values 0.476, 0.971, 0.509, 0.405, 0.122, 0.994, 0.892, and 0.418) respectively.ConclusionMost patients with breast cancer have positive expression of Ki67 which has a positive correlation with tumor grade, the presense of necrosis inside the tumor and estrogene receptor status. This marker is directly related with higher degrees of tumor agressiveness and may be useful in modulating different treatment modalities.