Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways
Background The introduction of effective novel biomarkers of invasion and metastasis is integral for the advancement of breast cancer management. The present study focused on the identification and evaluation of calreticulin (CRT) as a potential biomarker for breast cancer invasion. Methods Two...
Saved in:
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BioMed Central
2016
|
Online Access: | http://psasir.upm.edu.my/id/eprint/55230/1/Calreticulin%20mediates%20an%20invasive%20breast%20cancer%20phenotype%20through%20the%20transcriptional%20dysregulation%20of%20p53%20and%20MAPK%20pathways.pdf http://psasir.upm.edu.my/id/eprint/55230/ http://www.cancerci.com |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
my.upm.eprints.55230 |
---|---|
record_format |
eprints |
spelling |
my.upm.eprints.552302017-11-29T04:30:36Z http://psasir.upm.edu.my/id/eprint/55230/ Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways Zamanian, Mohammadreza Hamadneh, Lama Abdel Qader Veerakumarasivam, Abhi Abdul Rahman, Sabariah Shohaimi, Shamarina Rosli, Rozita Background The introduction of effective novel biomarkers of invasion and metastasis is integral for the advancement of breast cancer management. The present study focused on the identification and evaluation of calreticulin (CRT) as a potential biomarker for breast cancer invasion. Methods Two-dimensional gel protein electrophoresis and MALDI-TOF were utilized in the analysis of fresh-frozen invasive intra-ductal carcinoma specimens. Calreticulin-associated expression was analyzed using immunohistochemistry of FFPE non-malignant/malignant breast specimens. A CRT-knockdown model of MCF7 cell line was developed using siRNA and the CRT genotype/phenotype correlations based on migration and trans-well invasion assays were determined. Finally, microarray-based global gene expression profiling was conducted to elucidate the possible calreticulin pro-invasive regulatory pathways. Results Two-dimensional gel protein electrophoresis and MALDI-TOF analysis showed upregulation of calreticulin expression in tumor tissues as compared to the normal adjacent tissues. Meta-analysis of the immunohistochemical results confirmed significantly higher expression of calreticulin (p < 0.05) in the stromal compartments of malignant tissues as compared to non-malignant tissues. Migration and transwell invasion assays showed significant loss in the migratory and invasive potential of CRT-knockdown cells (p < 0.05). Global gene expression profiling successfully identified various putative gene networks such as p53 and MAPK pathways that are involved in calreticulin breast cancer signaling. Conclusion Besides confirming calreticulin overexpression in invasive breast cancer tissues, this study reveals a calreticulin-dependent pro-invasive potential and suggests possible contributing pathways. Defining the mechanistic role of invasion and characterizing the possible calreticulin-dependent molecular targets will be the focus of future work. BioMed Central 2016-07 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/55230/1/Calreticulin%20mediates%20an%20invasive%20breast%20cancer%20phenotype%20through%20the%20transcriptional%20dysregulation%20of%20p53%20and%20MAPK%20pathways.pdf Zamanian, Mohammadreza and Hamadneh, Lama Abdel Qader and Veerakumarasivam, Abhi and Abdul Rahman, Sabariah and Shohaimi, Shamarina and Rosli, Rozita (2016) Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways. Cancer Cell International, 16 (56). pp. 1-13. ISSN ESSN: 1475-2867 http://www.cancerci.com 10.1186/s12935-016-0329-y |
institution |
Universiti Putra Malaysia |
building |
UPM Library |
collection |
Institutional Repository |
continent |
Asia |
country |
Malaysia |
content_provider |
Universiti Putra Malaysia |
content_source |
UPM Institutional Repository |
url_provider |
http://psasir.upm.edu.my/ |
language |
English |
description |
Background
The introduction of effective novel biomarkers of invasion and metastasis is integral for the advancement of breast cancer management. The present study focused on the identification and evaluation of calreticulin (CRT) as a potential biomarker for breast cancer invasion.
Methods
Two-dimensional gel protein electrophoresis and MALDI-TOF were utilized in the analysis of fresh-frozen invasive intra-ductal carcinoma specimens. Calreticulin-associated expression was analyzed using immunohistochemistry of FFPE non-malignant/malignant breast specimens. A CRT-knockdown model of MCF7 cell line was developed using siRNA and the CRT genotype/phenotype correlations based on migration and trans-well invasion assays were determined. Finally, microarray-based global gene expression profiling was conducted to elucidate the possible calreticulin pro-invasive regulatory pathways.
Results
Two-dimensional gel protein electrophoresis and MALDI-TOF analysis showed upregulation of calreticulin expression in tumor tissues as compared to the normal adjacent tissues. Meta-analysis of the immunohistochemical results confirmed significantly higher expression of calreticulin (p < 0.05) in the stromal compartments of malignant tissues as compared to non-malignant tissues. Migration and transwell invasion assays showed significant loss in the migratory and invasive potential of CRT-knockdown cells (p < 0.05). Global gene expression profiling successfully identified various putative gene networks such as p53 and MAPK pathways that are involved in calreticulin breast cancer signaling.
Conclusion
Besides confirming calreticulin overexpression in invasive breast cancer tissues, this study reveals a calreticulin-dependent pro-invasive potential and suggests possible contributing pathways. Defining the mechanistic role of invasion and characterizing the possible calreticulin-dependent molecular targets will be the focus of future work. |
format |
Article |
author |
Zamanian, Mohammadreza Hamadneh, Lama Abdel Qader Veerakumarasivam, Abhi Abdul Rahman, Sabariah Shohaimi, Shamarina Rosli, Rozita |
spellingShingle |
Zamanian, Mohammadreza Hamadneh, Lama Abdel Qader Veerakumarasivam, Abhi Abdul Rahman, Sabariah Shohaimi, Shamarina Rosli, Rozita Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways |
author_facet |
Zamanian, Mohammadreza Hamadneh, Lama Abdel Qader Veerakumarasivam, Abhi Abdul Rahman, Sabariah Shohaimi, Shamarina Rosli, Rozita |
author_sort |
Zamanian, Mohammadreza |
title |
Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways |
title_short |
Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways |
title_full |
Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways |
title_fullStr |
Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways |
title_full_unstemmed |
Calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and MAPK pathways |
title_sort |
calreticulin mediates an invasive breast cancer phenotype through the transcriptional dysregulation of p53 and mapk pathways |
publisher |
BioMed Central |
publishDate |
2016 |
url |
http://psasir.upm.edu.my/id/eprint/55230/1/Calreticulin%20mediates%20an%20invasive%20breast%20cancer%20phenotype%20through%20the%20transcriptional%20dysregulation%20of%20p53%20and%20MAPK%20pathways.pdf http://psasir.upm.edu.my/id/eprint/55230/ http://www.cancerci.com |
_version_ |
1643835833767165952 |
score |
13.18916 |