MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in b...MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB- 231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR- 205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A （VEGF-A） are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3＇-untranslated region （3＇-UTR） of ErbB3 and VEGF-A. Together, these results suggest that miR- 205 is a tumor suppressor in breast cancer.展开更多
MicroRNAs （miRNAs） play an important role in carcinogenesis in various solid cancers including breast can-cer. Down-regulation of microRNA-148a （miR-148a） has been reported in certain cancer types. However, the bi...MicroRNAs （miRNAs） play an important role in carcinogenesis in various solid cancers including breast can-cer. Down-regulation of microRNA-148a （miR-148a） has been reported in certain cancer types. However, the biological role of miR-148a and its related targets in breast cancer are unknown yet. In this study, we showed that the level of miR-148a was lower in MCF7 cells than that in MCF10A cells. V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 （ERBB3） is a direct target of miR-148a in human breast cancer cells through direct binding of miR-148a to ERBB3 3’-UTR region. Overexpression of miR-148a in MCF7 cells inhibited ERBB3 expression, blocked the downstream pathway activation including activation of AKT, ERK1/2, and p70S6K1, and decreased HIF-1α expression. Furthermore, forced expression of miR-148a attenuated tumor angiogenesis in vivo. Our re-sults identify ERBB3 as a direct target of miR-148a, and provide direct evidence that miR-148a inhibits tumor an-giogenesis through ERBB3 and its downstream signaling molecules. This information would be helpful for target-ing the miR-148a/ERBB3 pathway for breast cancer prevention and treatment in the future.展开更多
Heregulin-α (HRGα) is a cytokine secreted by the mammary mesenchyme, adjacent to lobuloalveolar structures. To understand the role of HRGα and its receptors in mammary glands, and the underlying mechanisms, we perf...Heregulin-α (HRGα) is a cytokine secreted by the mammary mesenchyme, adjacent to lobuloalveolar structures. To understand the role of HRGα and its receptors in mammary glands, and the underlying mechanisms, we performed this study to determine the expression and localization of HRGα and its receptors ErbB2 and ErbB3. We also determined the role of HRGα in the development of mammary glands, β-casein expression and secretion, Rab3A protein expression and the phosphorylation of HRGα signaling molecules using confocal laser scanning microscopy, tissue culture, capillary electrophoresis, Western blotting and enzyme-linked immunosorbent assays. We found that a peak was on pregnancy day 15. Changes of ErbB2 and ErbB3 expression were positively and linearly correlated with HRGα, indicating that HRGα positively regulates ErbB2 and ErbB3 expression. During pregnancy, HRGα enhanced the phosphorylation of STAT5, p42/p44, p38, PKC and Rab3A protein expression, stimulated the proliferation and differentiation of the ductal epithelial cells of mammary glands, and increased and maintained the expression and secretion of β-casein. During lactation, HRGα enhanced the phosphorylation of STAT5 and p38, inhibited the phosphorylation of PKC and Rab3A protein expression, maintained the morphology of the mammary glands and increased the secretion of lactoprotein to reduce the expression of β-casein in mammary epithelial cells. During involution, HRGα induced the phosphorylation of STAT3 and Rab3A protein expression, and inhibited the phosphorylation of PKC to stimulate the degeneration of mammary epithelial cells. It also inhibited the secretion of β-casein, resulting in increased levels of β-casein in mammary epithelial cells.展开更多
Background Chronic obstructive pulmonary disease （COPD） is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha （TNF-α...Background Chronic obstructive pulmonary disease （COPD） is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha （TNF-α） is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-α converting enzyme （TACE） is involved in the activation of both TNF-α and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-α and ErbB3 and to explore the correlations among TACE,TNF-α and ErbB3 respectively. Methods Thirty Wistar male rats were randomly divided into COPD group （group C, n=10）, saline solution parallel group （group P, n=-8）, and normal control group （group N, n=-8）. Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in turn. The expressions of TACE, TNF-α and ErbB3 in lungs of all rats were determined histochemically. Results The expressions of TACE, TNF-α and ErbB3 were significantly higher in group C than in group N （P〈0.01）. The contents of TNF-α in serum （P〈0.01） and bronchoalveolar lavage fluid （BALF） （P〈0.01） were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-α （r=0.784, P〈0.01） and between TACE and ErbB3 （r=0.526, P〈0.01） respectively. Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-α and ErbB3.展开更多
Objective: To evaluate factors for prognosis of cervical carcinoma. Methods: Expressions of mn23- HI, erbB3 and erbB4 were examined by immunohistochemical staining. The apoptosis was detected in situ by the TdT mediat...Objective: To evaluate factors for prognosis of cervical carcinoma. Methods: Expressions of mn23- HI, erbB3 and erbB4 were examined by immunohistochemical staining. The apoptosis was detected in situ by the TdT mediated duip-biotin nick end-labeling (TUNEL) technique. Mitotic cell were counted by HE dyeing. Results: FIGO stage and lymph node metastasis were the most important factors for evaluating prognosis in adenocarcinoma or squamous cell carcinoma. AI/MI was positively correlated with 5-year survival of cervical carcinoma. Positive expression of nm23-H1 combed with negative expression of erbB4 [nm23-H1(+)/erbB4(?)] predicted good prognosis for adenocarcinoma. In multivariable Cox regression analysis, only FIGO stage and AI/MI were into equation. Conclusion: FIGO stage and AI/MI were independent evaluating parameter for adenocarcinoma or squamous cell carcinoma.展开更多
文摘MicroRNAs （miRNAs） are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB- 231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR- 205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A （VEGF-A） are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3＇-untranslated region （3＇-UTR） of ErbB3 and VEGF-A. Together, these results suggest that miR- 205 is a tumor suppressor in breast cancer.
基金supported by grants of the National Natural Science Foundation of China (No.30871296 and No.81071642)
文摘MicroRNAs （miRNAs） play an important role in carcinogenesis in various solid cancers including breast can-cer. Down-regulation of microRNA-148a （miR-148a） has been reported in certain cancer types. However, the biological role of miR-148a and its related targets in breast cancer are unknown yet. In this study, we showed that the level of miR-148a was lower in MCF7 cells than that in MCF10A cells. V-erb-b2 erythroblastic leukemia viral oncogene homolog 3 （ERBB3） is a direct target of miR-148a in human breast cancer cells through direct binding of miR-148a to ERBB3 3’-UTR region. Overexpression of miR-148a in MCF7 cells inhibited ERBB3 expression, blocked the downstream pathway activation including activation of AKT, ERK1/2, and p70S6K1, and decreased HIF-1α expression. Furthermore, forced expression of miR-148a attenuated tumor angiogenesis in vivo. Our re-sults identify ERBB3 as a direct target of miR-148a, and provide direct evidence that miR-148a inhibits tumor an-giogenesis through ERBB3 and its downstream signaling molecules. This information would be helpful for target-ing the miR-148a/ERBB3 pathway for breast cancer prevention and treatment in the future.
基金supported by the National High Technology Research and Development Program of China (Grant No. 2006AA10Z1A4)the grants from Innovation Team of the Northeast Agricultural University (Grant No. LXT005-1-1)
文摘Heregulin-α (HRGα) is a cytokine secreted by the mammary mesenchyme, adjacent to lobuloalveolar structures. To understand the role of HRGα and its receptors in mammary glands, and the underlying mechanisms, we performed this study to determine the expression and localization of HRGα and its receptors ErbB2 and ErbB3. We also determined the role of HRGα in the development of mammary glands, β-casein expression and secretion, Rab3A protein expression and the phosphorylation of HRGα signaling molecules using confocal laser scanning microscopy, tissue culture, capillary electrophoresis, Western blotting and enzyme-linked immunosorbent assays. We found that a peak was on pregnancy day 15. Changes of ErbB2 and ErbB3 expression were positively and linearly correlated with HRGα, indicating that HRGα positively regulates ErbB2 and ErbB3 expression. During pregnancy, HRGα enhanced the phosphorylation of STAT5, p42/p44, p38, PKC and Rab3A protein expression, stimulated the proliferation and differentiation of the ductal epithelial cells of mammary glands, and increased and maintained the expression and secretion of β-casein. During lactation, HRGα enhanced the phosphorylation of STAT5 and p38, inhibited the phosphorylation of PKC and Rab3A protein expression, maintained the morphology of the mammary glands and increased the secretion of lactoprotein to reduce the expression of β-casein in mammary epithelial cells. During involution, HRGα induced the phosphorylation of STAT3 and Rab3A protein expression, and inhibited the phosphorylation of PKC to stimulate the degeneration of mammary epithelial cells. It also inhibited the secretion of β-casein, resulting in increased levels of β-casein in mammary epithelial cells.
文摘Background Chronic obstructive pulmonary disease （COPD） is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha （TNF-α） is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-α converting enzyme （TACE） is involved in the activation of both TNF-α and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-α and ErbB3 and to explore the correlations among TACE,TNF-α and ErbB3 respectively. Methods Thirty Wistar male rats were randomly divided into COPD group （group C, n=10）, saline solution parallel group （group P, n=-8）, and normal control group （group N, n=-8）. Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in turn. The expressions of TACE, TNF-α and ErbB3 in lungs of all rats were determined histochemically. Results The expressions of TACE, TNF-α and ErbB3 were significantly higher in group C than in group N （P〈0.01）. The contents of TNF-α in serum （P〈0.01） and bronchoalveolar lavage fluid （BALF） （P〈0.01） were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-α （r=0.784, P〈0.01） and between TACE and ErbB3 （r=0.526, P〈0.01） respectively. Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-α and ErbB3.
文摘Objective: To evaluate factors for prognosis of cervical carcinoma. Methods: Expressions of mn23- HI, erbB3 and erbB4 were examined by immunohistochemical staining. The apoptosis was detected in situ by the TdT mediated duip-biotin nick end-labeling (TUNEL) technique. Mitotic cell were counted by HE dyeing. Results: FIGO stage and lymph node metastasis were the most important factors for evaluating prognosis in adenocarcinoma or squamous cell carcinoma. AI/MI was positively correlated with 5-year survival of cervical carcinoma. Positive expression of nm23-H1 combed with negative expression of erbB4 [nm23-H1(+)/erbB4(?)] predicted good prognosis for adenocarcinoma. In multivariable Cox regression analysis, only FIGO stage and AI/MI were into equation. Conclusion: FIGO stage and AI/MI were independent evaluating parameter for adenocarcinoma or squamous cell carcinoma.
