BRCA1 mutations contribute to cell motility and invasion by affecting its main regulators

Yasmeen, Amber; Li, Wenchao; Dekhil, Hafedh; Kassab, Amal; Aloyz, Raquel; Foulkes, William D.; Moustafa, Ala‐Eddin Al

doi:10.4161/cc.7.23.6993

Cited by 20 publications

(23 citation statements)

References 14 publications

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“…17,18 Inversely, loss of BRCA1 resulted in an increase in cell proliferation and a transition of cell cycle, 29,30 and contributed to breast cancer cell migration by affecting its main regulators, such as caveolin-1. 31,32 Our data in the present study revealed that the above-mentioned effects of EZH2 downregulation require the expression of BRCA1, as inhibition of BRCA1 partly rescued the decrease in cell proliferation, migration, and the delay in G 2 /M transition caused by EZH2 depletion. Consistently, preceding studies reported that EZH2 could modulate BRCA1-mediated cell proliferation in breast cancer.…”

Section: Discussionsupporting

confidence: 57%

EZH2 participates in malignant biological behavior of epithelial ovarian cancer through regulating the expression of BRCA1

Cai

et al. 2013

Cancer Biology & Therapy

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Section: Discussionsupporting

confidence: 57%

EZH2 participates in malignant biological behavior of epithelial ovarian cancer through regulating the expression of BRCA1

Cai

et al. 2013

Cancer Biology & Therapy

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“…Decreased BRCA1 expression in human sporadic breast cancer tissues is linked to the expression of cell cycle regulatory proteins 61. Yasmeen and colleagues have recently demonstrated for the first time that the BRCA1‐mutation deregulates the expression patterns of P‐cadherin, Caveolin‐1 as well as E‐cadherin 62. Furthermore, they also revealed that BRCA1 downregulates Id‐1 expression in human mammary epithelial cells 62.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells

Promkan

Patmasiriwat

Chakrabarty

2009

Intl Journal of Cancer

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BRCA1 is a multifunctional tumor-suppressive protein. Many functional aspects of BRCA1 are not fully understood. We used a shRNA approach to probe the function of BRCA1 in human breast cancer cells. Knocking down BRCA1 expression by shRNA in the wild-type BRCA1 human breast cancer MCF-7 and MDA-MB-231 cells resulted in an increase in cell proliferation, anchorage-independent growth, cell migration, invasion and a loss of p21/Waf1 and p27 Kip1 expression. In BRCA1 knocked-down cells, the expression of survivin was significantly up regulated with a concurrent decrease in cellular sensitivity to paclitaxel. We also found that cells harboring endogenous mutant or defective BRCA1 (MDA-MB-436 and HCC1937) were highly proliferative and expressed a relatively low level of p21/Waf1 and p27 Kip1 by comparison to wild-type BRCA1 cells. Cells harboring mutated BRCA1 also expressed a high level of survivin and were relatively resistant to paclitaxel by comparison to wild-type cells. Increase resistance to paclitaxel was due to an increase in the expression of survivin in both the BRCA1 knocked-down and mutant BRCA1 cells because knocking down survivin expression by siRNA restored sensitivity to paclitaxel. We conclude that BRCA1 down-modulates the malignant behavior of breast cancer cells, promotes the expression of p21/Waf1, p27 Kip1 and inhibits the expression of survivin. Moreover, loss of BRCA1 expression or function leads to an increase in survivin expression and a reduction in chemosensitivity to paclitaxel. ' UICCKey words: BRCA1; p21/Waf1; p27Kip1; survivin; chemosensitivity Hereditary breast cancer can be caused by germline mutations in 1 of the 2 tumor suppressor genes, BRCA1 and BRCA2 resulting in a loss of gene function. 1,2 Women carrying 1 mutated BRCA1 allele are at increased risk of developing breast cancer but tumor initiation requires a loss of the wild-type allele indicating that BRCA1 is a tumor suppressor gene. 3,4 Hereditary breast cancers account for 5-10% of all breast cancers. 5-8 Breast cancer cumulative risk to age 50 years and 70 years in mutation carriers are 49% and 71%, respectively, for BRCA1. 9 BRCA1 expression is also frequently reduced in sporadic cancer. 10-13 BRCA1 encodes an 1863 amino acid (220 kDa) protein that is targeted to the nucleus by 2 nuclear localization sequences, which interact with the nuclear transport signal receptor. 14-17 BRCA1 protein is multifunctional and interacts with other proteins in the nucleus in transcriptional regulation of gene expression, DNA repair and in the maintenance of genomic stability. 1,18 Thus, loss of BRCA1 function may lead to accumulation of chromosomal damage, abnormalities in growth control and tumorigenesis. 19 BRCA1 is regarded as an important central component in regulating multiple biological pathways. 18,20 The function of BRCA1 intersects with the cyclin-dependent kinase inhibitor p27 Kip1 , cyclin D1, the extracellular matrix [21][22][23] and with the estrogen and progesterone pathways in hormonal driven tumor development and progres...

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“…1). More contritely, restoration of BRCA1 and BRCA2 expression in these cell lines did not affect the ability of VSV to replicate in these cells; whereas the stable transfection of full length BRCA1 and BRCA2 cDNA restores cell cycle progression and blocks cell motility and invasion induced by these specific mutations in human primary breast and ovarian cells 7 ; and unpublished data in contrast, the control cells of human normal mammary epithelial cells expressing E6/E7 onco-proteins of HPV type 16 were killed by the VSV. In conclusion, our study shows clearly that VSV instillation therapy is questioned since the selective ability of this virus to kill cancer cells while sparing the normal cells is not confirmed, based on our study of matched normal and cancer cell lines established from the same patients; which suggests that VSV could replicate in normal as well as cancer cells in the majority of the cases.…”

Section: Dear Editormentioning

confidence: 79%

Does the vesicular stomatitis virus really have a selective oncolytic effect in human cancer?

Yasmeen

Zhang

Moustafa

2009

Intl Journal of Cancer

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BRCA1 mutations contribute to cell motility and invasion by affecting its main regulators

Abstract: (2008) BRCA1 mutations contribute to cell motility and invasion by affecting its main regulators, Cell Cycle, 7:23, 3781-3783,

Cited by 20 publications

References 14 publications

EZH2 participates in malignant biological behavior of epithelial ovarian cancer through regulating the expression of BRCA1

EZH2 participates in malignant biological behavior of epithelial ovarian cancer through regulating the expression of BRCA1

BRCA1 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells

Does the vesicular stomatitis virus really have a selective oncolytic effect in human cancer?

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