Expression and significance of LAT1 and p-s6 breast cancer / 临床与实验病理学杂志

Purpose To investigate the expression and significance of type L amino acid transporter 1 (LAT1 ) and phosphorylated s6 ribosomal protein (p-s6) in breast cancer tissues and their correlation. Methods LAT1 protein and p-s6 protein were detected by immunohistochemical EnVision two step method in 178 cases of breast cancer and 78 cases of benign breast lesion, and the relationship between the expression and clinicopathological parameters was analyzed. Results The positive rate of LAT1 in breast cancer was 36.5％, which was significantly higher than that of breast benign lesion tissues (23.1 ％, P＜ 0.05 ), the positive rate of p-s6 in breast cancer tissues was33.2％, which was significantly higher than that of breast benign lesion tissues (12.8％, P＜0.05). There was a positive correlation between the expression of LAT1 protein and p-s6 protein in breast cancer tissues (r = 0.345, P＜ 0.05). The expression of LAT1 protein in breast cancer was correlated with tumor diameter, axillary lymph node metastasis, TNM staging and HER-2 level (P＜ 0.05), but not associated with the patient's age, histological grade, ER, and PR levels (P＞ 0.05). The expression of p-s6 protein was related to axillary lymph node metastasis, TNM staging, age and ER level (P＜ 0.05), but not associated with tumor diameter, histological grade, PR and HER-2 levels (P＞ 0.05 ). Multivariate analysis showed that the expres sion of LAT1 protein was related to tumor diameter and expression level of HER-2. The expression of p-s6 protein was related to axillary lymph node metastasis. Conclusion The expression of LAT1 protein and p-s6 protein in breast cancer is up-regulated, and the expression of these two proteins is positively related, which implying that LAT1 and p-s6 might play a synergistic role in the development and progression of breast cancer.

Effect of silencing CD98hc expression on MDA-MB-231 breast cancer cells proliferation and invasion / 临床与实验病理学杂志

Purpose To investigate the effect of silencing of CD98hc on proliferation,migration and invasion of MDA-MB-231 breast cancer cells.Methods RNA interfere technology was used to silence CD98hc in MDA-MB-231 cells.MDA-MB-231 cells (CD98hc-shRNA) with stable low expression of CD98hc and Vector control was obtained.Western blot and qRT-PCR were used to verify the down-regulation of CD98hc.MTT assay was used to test the cell proliferation.Transwell migration and invasion experiment were used to assay cell migration and invasion.Results The expression levels of CD98hc was down-regulated by CD98hc-shRNA in the MDA-MB-231 breast cancer cells.Compared to that of blank cells (0.706 ± 0.013),vector control (0.724 ± 0.018),the cell proliferation potency of CD98hc-shRNA cells (0.580-0.035) was significantly inhibited (P ＜ 0.05),and the cell migration and invasion potency also were inhibited (P ＜ 0.05),there is on significant different between blank cells and vector control (P ＜ 0.05).Conclusion CD98hc might be involved in the regulation of breast cancer cell biological behaviors.

Prolactin Inhibits BCL6 Expression in Breast Cancer Cells through a MicroRNA-339-5p-Dependent Pathway / 한국유방암학회지

PURPOSE: Prolactin (PRL) plays a critical role in breast cancer progression by activating its cognate receptor and promotes the growth and differentiation of breast cancer cells. Studies have shown that B-cell lymphoma 6 (BCL6) is the target gene of microRNA-339-5p (miR-339-5p) and that BCL6 expression contributes to breast cancer progression. Herein, we identified PRL as a potent suppressor of BCL6 expression in human breast cancer cells. METHODS: Western blotting and quantitative reverse transcription-polymerase chain reaction were used to investigate molecular mechanisms underlying miR-339-5p expression and BCL6 manipulation in MCF-7, T47D, and SKBR3 breast cancer cells. Phenotypic changes in these breast cancer cell lines were assessed by performing cell viability (MTT), colony formation, migration, and invasion assays. RESULTS: PRL suppressed BCL6 protein and mRNA expression and upregulated miR-339-5p expression in MCF-7 and T47D breast cancer cells. Selective downregulation of miR-339-5p expression significantly reversed PRL-induced suppression of BCL6 mRNA and protein expression. Exogenous PRL stimulation significantly decreased the proliferation, colony formation, migration, and invasion of breast cancer cells, and suppression of miR-339-5p expression reversed these processes in vitro. CONCLUSION: These results indicated that PRL inhibited BCL6 expression and regulated breast cancer progression through a miR-339-5p-dependent pathway.

Expression of the LC3A protein in prostate cancer and its implications / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the expression of the LC3A protein in prostate cancer (PCa) and its clinicopathological significance. We detected the expression of the LC3A protein by immunohistochemistry in 54 cases of PCa and 14 cases of benign prostatic hyperplasia (BPH), and analyzed the correlation between the LC3A expression and the clinicopathological parameters in PCa. The positive signals of the LC3A protein were located in the cytoplasm and/or cell nuclei. The rate of its strongly positive expression was 90.7% in PCa, significantly higher than 14.3% in BPH (P < 0.01). The LC3A expression was also found in the cell nuclei of 22 cases of PCa, with no significant correlation to that in the cytoplasm (P > 0.05). The expression of LC3A was significantly correlated with Gleason scores (r = 0.297, P = 0.029 in cytoplasm; r = 0.288, P = 0.034 in cell nuclei), but not with the clinical stage, patient's age, androgen receptor (AR) level and preoperative levels of serum PSA and cPSA (all P > 0.05). LC3A was also expressed in the fibrocytes and smooth muscle cells in PCa and BPH. The positive rate of AR was 74.1% (40/54) in PCa and 64.3% (9/14) in BPH, with no significant difference between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>The expression of the LC3A protein might be involved in the development, differentiation, and prognosis of prostate cancer.</p>

Expression of TGF-beta1 and the mechanism of invasiveness and metastasis induced by TGF-beta1 in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of MMP-2, TIMP-2, TGF-beta1 and TGF-betaRI and the relationship among them in breast cancer.</p><p><b>METHODS</b>The protein expression of MMP-2, TIMP-2, TGF-beta1 and TGF-betaRI was detected on tissue chips by S-P immunohistochemical staining in 160 cases of breast carcinoma.</p><p><b>RESULTS</b>The positive rates of TGF-beta1, TGF-beta1 mRNA, MMP-2, MMP-9, TIMP-1 and TIMP-2 expression were 73.7%, 56.2%, 96.9%, 95.0%, 87.5% and 89.4%, respectively. Axillary lymph node metastasis and TNM staging (P < 0.01 and P < 0.01, respectively) were positively correlated to the expression of TGF-beta1. Relase-free survival of TGF-beta1 positive group was lower than that of TGF-beta1 negative group (P = 0.023). The expression of MMP-2 or MMP-9 was positively correlated to that of TGF-beta1 (r = 0.170, P < 0.05; r = 0.221, P < 0.01) and was negatively correlated to that of TGF-beta1 mRNA (r = -0.126, P > 0.05;r = 0.019, P > 0.05).</p><p><b>CONCLUSION</b>The expression of TGF-beta1 may be closely correlated with the invasion and metastasis of breast cancer. TGF-beta1-induced invasiveness and metastasis of breast cancer cells are mediated by MMP-2 and MMP-9.</p>

Expression of CD147, matrix metalloproteinases and transforming growth factor beta1 in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of CD147, matrix metalloproteinase (MMP)-2, MMP-9, Transforming growth factor (TGFbeta1) and TGFbetaRI proteins and their relationships to breast cancer.</p><p><b>METHODS</b>The expression of CD147, MMP-2, MMP-9, TGFbeta1 and TGFbetaRI proteins was examined on tissue chips containing 160 cases of breast carcinomas by S-P immunohistochemical method.</p><p><b>RESULTS</b>The positive rates of CD147, MMP-2, MMP-9, TGFbeta1 and TGFbetaRI proteins were 87.5% (140/160), 96.9% (155/160), 95.0% (152/160), 73.7% (118/160) and 60.6% (97/160), respectively. The expression of CD147 was positively correlated with axillary lymph node metastasis, TNM staging and HER2 over expression (P < 0.01, P < 0.05 and P < 0.01, respectively), and inversely correlated with PR expression (P < 0.05). The patients' relapse-free survival was shorter in TGFbeta1-positive group than in TGFbeta1 negative group (P < 0.05). Both the expression of MMP-2 and MMP-9 were positively correlated with CD147 expression; and both the expression of TGFbeta1 and TGFbetaRI were positively correlated with CD147 expression (P < 0.01 and P < 0.05, respectively).</p><p><b>CONCLUSION</b>The expression of CD147 is considered closely correlated with tumor invasion, metastasis and prognosis in breast cancer, and has also a close correlation with MMP-2, MMP-9, TGFbeta1 and TGFbetaRI expression.</p>

Expression of a novel metastasis-inducing protein human anterior gradient-2 (AGR2) in breast cancer and its clinical and prognostic significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of a novel metastasis-inducing protein human anterior gradient-2 (AGR2) in breast cancer and its clinical and prognostic significance.</p><p><b>METHODS</b>AGR2 expression was assessed in 160 cases of breast cancer and 20 cases of benign breast diseases by immunohistochemistry using tissue chip technology. In addition the expression of ERa, PR and c-erbB-2 in breast cancer was also evaluated. Follow-up information of 5-year duration was available in 127 patients with breast cancer. Kaplan-Meier analysis and COX regression model were used to analyze the correlation between AGR2 expression and the follow-up clinical data.</p><p><b>RESULTS</b>The expression of AGR2 was significantly higher in breast cancers than that in benign diseases (68.3% vs. 25.0% , P < 0.01). There was a negative correlation between AGR2 expression and the histological grade of breast cancer (P <0.05) , whereas positive correlations was found between the expression of AGR2 and ERalpha (P <0.05), and between the expression of AGR2 and PR (P <0.01). In the subgroup of ERalpha-positive breast cancer, Logistic regression model demonstrated AGR2 and TNM stage were important factors affecting lymph node metastasis (both P < 0.01). Kaplan-Meier analysis demonstrated that a positive expression of AGR2 was associated with poor overall survival and relapse-free survival (both P <0.01). Moreover, COX regression model confirmed the expression of AGR2 as an independent prognostic factor among patients with ERa-positive breast cancer (P <0.01).</p><p><b>CONCLUSIONS</b>The abnormal expression of AGR2 may play a role in the pathogenesis and progression of breast cancer. The metastasis-inducing capability of AGR2 may be partly regulated through the ER pathway. Therefore, AGR2 may be a useful molecular marker for prognostication for patient with hormone-responsive breast cancer.</p>