Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.

Background. B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various cancer such as non-small cell lung cancer, colon cancer, gastric cancer, bladder cancer and nasopharyngeal cancer (NPC). === Methods. Immunohistochemistry was performed to evaluate Bmi-1 ex...

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Other Authors: Guo, Baohong
Format: Others
Language:English
Chinese
Published: 2010
Subjects:
Online Access:http://library.cuhk.edu.hk/record=b6075058
http://repository.lib.cuhk.edu.hk/en/item/cuhk-344691
id ndltd-cuhk.edu.hk-oai-cuhk-dr-cuhk_344691
record_format oai_dc
collection NDLTD
language English
Chinese
format Others
sources NDLTD
topic Breast--Cancer--Genetic aspects
Tumor proteins
Breast Neoplasms--genetics
Proto-Oncogene Proteins--metabolism
spellingShingle Breast--Cancer--Genetic aspects
Tumor proteins
Breast Neoplasms--genetics
Proto-Oncogene Proteins--metabolism
Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.
description Background. B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various cancer such as non-small cell lung cancer, colon cancer, gastric cancer, bladder cancer and nasopharyngeal cancer (NPC). === Methods. Immunohistochemistry was performed to evaluate Bmi-1 expression in 252 breast cancer samples. The correlations were analyzed between Bmi-1 expression and clinicopathologic parameters, including age, tumor size, lymph nodal involvement, distant metastasis, clinical stages, hormone receptor (ER, PR) and Human Epidermal Growth Factor Receptor 2 (HER-2). The overall survivals were compared by Kaplan-Meier analysis based on Bmi-1 expression. === Results. Bmi-1 expression was significantly increased in primary cancer tissues than in matched adjacent non-cancerous tissues ( P<0.001). Only 35.9% (14 of 39) of adjacent non-cancerous tissues displayed high expression compared with 72.2% (182 of 252) in primary cancer tissues. Among adjacent non-cancerous tissues, no Bmi-1 staining signal was detected in 30.8% (12 in 39) samples. Only 28.2% (11 in 39) samples showed nucleus staining and the remaining 41.0% (16 in 39) samples exhibited cytoplasm staining. Of those cancer tissues, however, 75.4% (190 in 252) was stained in the nucleus and 24.6% (62 in 252) located in the cytoplasm. The elevated Bmi-1 expression was correlated with advanced clinicopathologic classifications (T, N, M) and clinical stages (P<0.001, respectively). A high level of Bmi-1 expression displayed unfavorable overall survival ( P<0.001). The overall survival rate, assessed by the Kaplan-Meier method, was 85.1% (57 in 67) in low Bmi-1 expression group, whereas it was only 59.9% (103 in 172) in high Bmi-1 expression group. In addition, Bmi-1 serves as a high risk for breast cancer and the relative risk increased almost four fold in patients with high Bmi-1 expression compared with that with low Bmi-1 expression by univariate Cox regression analyses. After the adjustment of the confounding factors, Bmi-1 was still found to predict the poor survival (P=0.042), which indicated Bmi-1 was an independent prognostic factor. The overexpression of Bmi-1 increased the mobility and invasiveness in 76N-TERT and MCF-10A, concurrent EMT-like molecular changes, the stabilization of Snail protein and the activation of Akt/GSK3beta pathway. Consistent with these observations, the repression of Bmi-1 in MDA-MB-435S remarkably attenuated the cellular mobility, invasiveness and transformation, as well as tumorigenesis and spontaneous lung metastases in nude mice. In addition, the repression of Bmi-1 reversed the EMT markers and inhibited the Akt/GSK3beta/Snail pathway. However, ectopic Bmi-1 alone was not able to lead to the phenotype of HMECs. Additionally, discordant mRNA expression levels of Bmi-1 and E-cadherin were detected between primary cancer tissues and matched adjacent non-cancerous tissues. The mRNA level of Bmi-1 was strongly up-regulated in breast cancer tissues compared with paired non-cancerous tissues ( P=0.001), whereas the mRNA level of E-cadherin was markedly down-regulated (P=0.042). Furthermore, there was a converse correlation between Bmi-1 and E-cadherin expression at the transcriptional level ( P=0.041). (Abstract shortened by UMI.) === Guo, Baohong. === Adviser: Kung, Hsiang Fu. === Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . === Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. === Includes bibliographical references (leaves 161-183). === Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. === Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. === Abstract also in Chinese.
author2 Guo, Baohong
author_facet Guo, Baohong
title Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.
title_short Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.
title_full Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.
title_fullStr Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.
title_full_unstemmed Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.
title_sort bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer.
publishDate 2010
url http://library.cuhk.edu.hk/record=b6075058
http://repository.lib.cuhk.edu.hk/en/item/cuhk-344691
_version_ 1718977977586286592
spelling ndltd-cuhk.edu.hk-oai-cuhk-dr-cuhk_3446912019-02-19T03:42:41Z Bmi-1 promotes the invasion and metastasis and its elevated expression is correlated with advanced stage of breast cancer. CUHK electronic theses & dissertations collection Breast--Cancer--Genetic aspects Tumor proteins Breast Neoplasms--genetics Proto-Oncogene Proteins--metabolism Background. B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various cancer such as non-small cell lung cancer, colon cancer, gastric cancer, bladder cancer and nasopharyngeal cancer (NPC). Methods. Immunohistochemistry was performed to evaluate Bmi-1 expression in 252 breast cancer samples. The correlations were analyzed between Bmi-1 expression and clinicopathologic parameters, including age, tumor size, lymph nodal involvement, distant metastasis, clinical stages, hormone receptor (ER, PR) and Human Epidermal Growth Factor Receptor 2 (HER-2). The overall survivals were compared by Kaplan-Meier analysis based on Bmi-1 expression. Results. Bmi-1 expression was significantly increased in primary cancer tissues than in matched adjacent non-cancerous tissues ( P<0.001). Only 35.9% (14 of 39) of adjacent non-cancerous tissues displayed high expression compared with 72.2% (182 of 252) in primary cancer tissues. Among adjacent non-cancerous tissues, no Bmi-1 staining signal was detected in 30.8% (12 in 39) samples. Only 28.2% (11 in 39) samples showed nucleus staining and the remaining 41.0% (16 in 39) samples exhibited cytoplasm staining. Of those cancer tissues, however, 75.4% (190 in 252) was stained in the nucleus and 24.6% (62 in 252) located in the cytoplasm. The elevated Bmi-1 expression was correlated with advanced clinicopathologic classifications (T, N, M) and clinical stages (P<0.001, respectively). A high level of Bmi-1 expression displayed unfavorable overall survival ( P<0.001). The overall survival rate, assessed by the Kaplan-Meier method, was 85.1% (57 in 67) in low Bmi-1 expression group, whereas it was only 59.9% (103 in 172) in high Bmi-1 expression group. In addition, Bmi-1 serves as a high risk for breast cancer and the relative risk increased almost four fold in patients with high Bmi-1 expression compared with that with low Bmi-1 expression by univariate Cox regression analyses. After the adjustment of the confounding factors, Bmi-1 was still found to predict the poor survival (P=0.042), which indicated Bmi-1 was an independent prognostic factor. The overexpression of Bmi-1 increased the mobility and invasiveness in 76N-TERT and MCF-10A, concurrent EMT-like molecular changes, the stabilization of Snail protein and the activation of Akt/GSK3beta pathway. Consistent with these observations, the repression of Bmi-1 in MDA-MB-435S remarkably attenuated the cellular mobility, invasiveness and transformation, as well as tumorigenesis and spontaneous lung metastases in nude mice. In addition, the repression of Bmi-1 reversed the EMT markers and inhibited the Akt/GSK3beta/Snail pathway. However, ectopic Bmi-1 alone was not able to lead to the phenotype of HMECs. Additionally, discordant mRNA expression levels of Bmi-1 and E-cadherin were detected between primary cancer tissues and matched adjacent non-cancerous tissues. The mRNA level of Bmi-1 was strongly up-regulated in breast cancer tissues compared with paired non-cancerous tissues ( P=0.001), whereas the mRNA level of E-cadherin was markedly down-regulated (P=0.042). Furthermore, there was a converse correlation between Bmi-1 and E-cadherin expression at the transcriptional level ( P=0.041). (Abstract shortened by UMI.) Guo, Baohong. Adviser: Kung, Hsiang Fu. Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. Includes bibliographical references (leaves 161-183). Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. Abstract also in Chinese. Guo, Baohong Chinese University of Hong Kong Graduate School. Division of Public Health. 2010 Text theses electronic resource microform microfiche 1 online resource (xxii, 183 leaves : ill.) cuhk:344691 isbn: 9781267003935 http://library.cuhk.edu.hk/record=b6075058 eng chi Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) http://repository.lib.cuhk.edu.hk/en/islandora/object/cuhk%3A344691/datastream/TN/view/Bmi-1%20promotes%20the%20invasion%20and%20metastasis%20and%20its%20elevated%20expression%20is%20correlated%20with%20advanced%20stage%20of%20breast%20cancer.jpghttp://repository.lib.cuhk.edu.hk/en/item/cuhk-344691