Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer

BMC Medicine

Research Article

Kathy Q Cai¹  Andrew K Godwin²  Callinice D Capo-chichi³  Xiang-Xi Xu⁴  Fiona Simpkins⁵  Parvin Ganjei-Azar⁶ 

[1] Ovarian Cancer Program, Fox Chase Cancer Center, 19111, Philadelphia, PA, USA;Ovarian Cancer Program, Fox Chase Cancer Center, 19111, Philadelphia, PA, USA;Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 66160, Kansas City, KS, USA;Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Department of Medicine, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Department of Medicine, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Department of Obstetrics and Gynecology, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Department of Obstetrics and Gynecology, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;Department of Pathology, University of Miami Miller School of Medicine, 33136, Miami, FL, USA;

关键词: Ovarian Cancer;    Ovarian Cancer Cell;    Nuclear Envelope;    Nuclear Morphology;    Aneuploid Cell;   

DOI  :  10.1186/1741-7015-9-28

 received in 2011-01-28, accepted in 2011-03-26,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundDespite our substantial understanding of molecular mechanisms and gene mutations involved in cancer, the technical approaches for diagnosis and prognosis of cancer are limited. In routine clinical diagnosis of cancer, the procedure is very basic: nuclear morphology is used as a common assessment of the degree of malignancy, and hence acts as a prognostic and predictive indicator of the disease. Furthermore, though the atypical nuclear morphology of cancer cells is believed to be a consequence of oncogenic signaling, the molecular basis remains unclear. Another common characteristic of human cancer is aneuploidy, but the causes and its role in carcinogenesis are not well established.MethodsWe investigated the expression of the nuclear envelope proteins lamin A/C in ovarian cancer by immunohistochemistry and studied the consequence of lamin A/C suppression using siRNA in primary human ovarian surface epithelial cells in culture. We used immunofluorescence microscopy to analyze nuclear morphology, flow cytometry to analyze cellular DNA content, and fluorescence in situ hybridization to examine cell ploidy of the lamin A/C-suppressed cells.ResultsWe found that nuclear lamina proteins lamin A/C are often absent (47%) in ovarian cancer cells and tissues. Even in lamin A/C-positive ovarian cancer, the expression is heterogeneous within the population of tumor cells. In most cancer cell lines, a significant fraction of the lamin A/C-negative population was observed to intermix with the lamin A/C-positive cells. Down regulation of lamin A/C in non-cancerous primary ovarian surface epithelial cells led to morphological deformation and development of aneuploidy. The aneuploid cells became growth retarded due to a p53-dependent induction of the cell cycle inhibitor p21.ConclusionsWe conclude that the loss of nuclear envelope structural proteins, such as lamin A/C, may underlie two of the hallmarks of cancer - aberrations in nuclear morphology and aneuploidy.

【 授权许可】

Unknown   
© Capo-chichi et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.