Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer

Through advances in technology, the genetic basis of cancer has been investigated at the genomic level, and many fundamental questions have begun to be addressed. Among several key unresolved questions in cancer biology, the molecular basis for the link between nuclear deformation and malignancy has...

Full description

Bibliographic Details
Main Authors:	Capo-chichi, Callinice D., Cai, Kathy Q., Smedberg, Jennifer, Ganjei-Azar, Parvin, Godwin, Andrew K., Xu, Xiang-Xi
Format:	Online
Language:	English
Published:	Sun Yat-sen University Cancer Center 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941915/

id	pubmed-3941915
recordtype	oai_dc
spelling	pubmed-39419152014-03-04 Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer Capo-chichi, Callinice D. Cai, Kathy Q. Smedberg, Jennifer Ganjei-Azar, Parvin Godwin, Andrew K. Xu, Xiang-Xi Original Article Through advances in technology, the genetic basis of cancer has been investigated at the genomic level, and many fundamental questions have begun to be addressed. Among several key unresolved questions in cancer biology, the molecular basis for the link between nuclear deformation and malignancy has not been determined. Another hallmark of human cancer is aneuploidy; however, the causes and consequences of aneuploidy are unanswered and are hotly contested topics. We found that nuclear lamina proteins lamin A/C are absent in a significant fraction (38%) of human breast cancer tissues. Even in lamin A/C–positive breast cancer, lamin A/C expression is heterogeneous or aberrant (such as non-nuclear distribution) in the population of tumor cells, as determined by immunohistology and immunofluorescence microscopy. In most breast cancer cell lines, a significant fraction of the lamin A/C– negative population was observed. To determine the consequences of the loss of lamin A/C, we suppressed their expression by shRNA in non-cancerous primary breast epithelial cells. Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation, resembling that of cancer cells, as observed by immunofluorescence microscopy. The lamin A/C–suppressed breast epithelial cells developed aneuploidy as determined by both flow Cytometry and fluorescence in situ hybridization. We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy. Sun Yat-sen University Cancer Center 2011-06 /pmc/articles/PMC3941915/ /pubmed/21627864 http://dx.doi.org/10.5732/cjc.010.10566 Text en Chinese Journal of Cancer http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Capo-chichi, Callinice D. Cai, Kathy Q. Smedberg, Jennifer Ganjei-Azar, Parvin Godwin, Andrew K. Xu, Xiang-Xi
spellingShingle	Capo-chichi, Callinice D. Cai, Kathy Q. Smedberg, Jennifer Ganjei-Azar, Parvin Godwin, Andrew K. Xu, Xiang-Xi Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer
author_facet	Capo-chichi, Callinice D. Cai, Kathy Q. Smedberg, Jennifer Ganjei-Azar, Parvin Godwin, Andrew K. Xu, Xiang-Xi
author_sort	Capo-chichi, Callinice D.
title	Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer
title_short	Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer
title_full	Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer
title_fullStr	Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer
title_full_unstemmed	Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer
title_sort	loss of a-type lamin expression compromises nuclear envelope integrity in breast cancer
description	Through advances in technology, the genetic basis of cancer has been investigated at the genomic level, and many fundamental questions have begun to be addressed. Among several key unresolved questions in cancer biology, the molecular basis for the link between nuclear deformation and malignancy has not been determined. Another hallmark of human cancer is aneuploidy; however, the causes and consequences of aneuploidy are unanswered and are hotly contested topics. We found that nuclear lamina proteins lamin A/C are absent in a significant fraction (38%) of human breast cancer tissues. Even in lamin A/C–positive breast cancer, lamin A/C expression is heterogeneous or aberrant (such as non-nuclear distribution) in the population of tumor cells, as determined by immunohistology and immunofluorescence microscopy. In most breast cancer cell lines, a significant fraction of the lamin A/C– negative population was observed. To determine the consequences of the loss of lamin A/C, we suppressed their expression by shRNA in non-cancerous primary breast epithelial cells. Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation, resembling that of cancer cells, as observed by immunofluorescence microscopy. The lamin A/C–suppressed breast epithelial cells developed aneuploidy as determined by both flow Cytometry and fluorescence in situ hybridization. We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.
publisher	Sun Yat-sen University Cancer Center
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941915/
_version_	1612064132988665856

Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer

Similar Items