Correlation Between Raf/MEK/ERK Signaling Pathway and Clinicopathological Features and Prognosis for Patients With Breast Cancer Having Axillary Lymph Node Metastasis.

OBJECTIVE: This study aims to investigate the correlations between rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase signaling pathway and clinicopathological features and prognosis for patients with breast cancer having axillary lymph node metastasis. METHODS: A total of 118 breast cancer tissues with axillary lymph node metastasis (axillary lymph node metastasis group), 150 breast cancer tissues with non-axillary lymph node metastasis (non-axillary lymph node metastasis group), and 216 normal breast tissues (normal group) were enrolled in this study. The messenger RNA and protein expressions of rapidly accelerated fibrosarcoma, MEK, extracellular signal-regulated kinase, and their phosphorylated (p-) proteins were examined by reverse transcriptase quantitative polymerase chain reaction and immunohistochemistry, respectively. All patients received a 1-year follow-up, and the clinical follow-up data were collected. The multiple factors on the prognosis of patients with breast cancer having axillary lymph node metastasis were tested by Cox regression analysis. RESULTS: The messenger RNA expressions of rapidly accelerated fibrosarcoma, MEK, and extracellular signal-regulated kinase and positive rates of rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and p-extracellular signal-regulated kinase in the axillary lymph node metastasis group were higher than in the non-axillary lymph node metastasis and normal groups (all P < .05). The protein expressions of rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and p-extracellular signal-regulated kinase were associated with tumor size, clinical stage, and axillary lymph node metastasis number (all P < .05). Rapidly accelerated fibrosarcoma, MEK, and extracellular signal-regulated kinase expressions were significantly correlated with the prognosis of patients with breast cancer (all P < .05). Patients with BC having positive rapidly accelerated fibrosarcoma, MEK, phosphorylated MEK, extracellular signal-regulated kinase, and phosphorylated ERK expressions had a higher survival rate than patients with BC having the negative ones (all P < .05). Rapidly accelerated fibrosarcoma and extracellular signal-regulated kinase protein expressions, clinical stage, pathological grade, and axillary lymph node metastasis number were independent prognostic factors in patients with breast cancer having axillary lymph node metastasis (all P < .05). CONCLUSION: Our study proved that rapidly accelerated fibrosarcoma/MEK/extracellular signal-regulated kinase signaling pathway is significantly correlated with the clinicopathological features and prognosis for patients with BC having axillary lymph node metastasis. Rapidly accelerated fibrosarcoma and extracellular signal-regulated kinase protein expressions are independent prognostic factors for patients with breast cancer having axillary lymph node metastasis.

[A preliminary functional study of AT motif binding factor 1 in colorectal cancer].

OBJECTIVE: To investigate the function of AT motif binding factor 1 (ATBF1) in colorectal cancer. METHDS: ATBF1 protein expression was detected in 146 pairs of colorectal cancer tissues and the adjacent tissues using immunohistochemistry. ATBF1 protein expression was also examined in colorectal cell lines with laser confocal microscopy. ATBF1-A protein expression in colorectal cancer tissues of different differentiation grades and in the colorectal cancer cell lines were detected with Western blotting. The expressions of ATBF1 mRNA in 38 moderately differentiated colorectal cancer tissues and the paired adjacent tissues and in the colorectal cancer cell lines were tested using RT-PCR. RESULTS: ATBF1 protein expression levels in colorectal cancer tissues and adjacent tissues differed significantly (P<0.001), and its expression increased significantly in positive correlation with the grade of tumor differentiation (P<0.001) but in negative correlation with tumor metastasis. ATBF1 mRNA expression and ATBF1 protein expression were significantly correlated (P=0.100). The ATBF1 protein and mRNA expressions also differed significantly among different colorectal cancer cell lines. CONCLUSION: ATBF1 executes the role of a tumor suppressor gene in colorectal cancer, and its protein expression is associated with tumor differentiation and lymph node metastases.

Autophagic regulation of cell growth by altered expression of Beclin 1 in triple-negative breast cancer.

Beclin 1 is a promoter gene for autophagy as well as a key factor for regulating tumor cell growth and death. Allelic deletion of Beclin 1 has been observed in certain triple-negative breat cancer (TNBC) cells, and it might be associated with increased proliferation and invasion in TNBC cells. In this study we investigated the relationship between Beclin 1 expression and prognosis for TNBC patients, as well as the influence on cell growth by Beclin 1 overexpression in different cultural conditions. Beclin 1 expression in TNBC tissues was measured by immunohistochemical staining and correlated with clinicopathologic parameters for TNBC patients. The plasmid of pDS-RED-C1-Beclin 1 was transfected to BT-549 and MDA-MB-231 cells and autophagy, proliferation, apoptosis, cell cycle and Epithelial-mesenchymal transition (EMT) process were measured. Results indicated that high level of Beclin 1 expression was correlated with more lymph nodes and distant metastasis but unrelated to survival rates in 5 years for TNBC patients. In vitro, overexpression of Beclin 1 improved cellular autophagy in both BT-549 and MDA-MB-231 cells, inhibited cell proliferation at normal cultural condition and increased cell survival in starvation, hypoxia or with doxorubicin stimulation. Besides, Beclin 1 overexpression decreased cell apoptosis, induced cells to be in G0/G1 phase and promoted EMT process through Wnt/ß-catenin pathway in starvation. Thus, Beclin 1 overexpression plays a double role in BT-549 and MDA-MB-231 cell growth by elevating the capability of autophagy. These findings might be useful for searching a proper method for clinical therapy of TNBC from the aspect of autophagy in future.