211 BRCA1 functions as a differential modulator of chemotherapy induced apoptosis

Quinn, JE; Kennedy, R. D.; Pb, Mullan; Johnston, P. G.; Harkin, D. Paul

doi:10.1016/s1359-6349(04)80219-2

Cited by 213 publications

(323 citation statements)

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“…By using Brca1-deficient or Brca1-proficient cells, we showed that Brca1-silenced cells were more prone to bypass the G 2 -M checkpoint and accumulate at mitosis, whereas Brca1-proficient cell types would be more stringently G 2 -M arrested when subjected to 17-AAG. Observation confirmed with previous studies using other drugs such as paclitaxel, vinorelbine, bleomycin (26), and genistein (27) and more recently by Yamane et al (19) that has suggested that Brca1 may influence G 2 -M checkpoint response to 6-thioguanine.…”

Section: Discussionsupporting

confidence: 87%

Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in BRCA1-deficient breast cancer cell lines

Zając¹,

Moneo

Carnero

et al. 2008

Molecular Cancer Therapeutics

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Heat shock protein 90 (Hsp90) is a molecular chaperone involved in folding, assembly, maturation, and stabilization of the client proteins that regulate survival of malignant cells. As previous reports correlate high Hsp90 expression with decreased survival in breast cancer, Hsp90 may be a favorable target for investigational therapy in breast cancer. In our study, we have examined the response of a panel of both BRCA1-null (UACC 3199, HCC 1937, and MBA-MD-436) and BRCA1-wt breast cancer cell lines (MCF-7, MBA-MD-157, and Hs578T) to determine the proteins governing response to Hsp90 inhibitor 17-allyloamino-17-demethoxy-geldanamycin. On treatment with the drug, cells arrested at G 2 -M phase and entered aberrant mitosis in a BRCA1-dependent manner. Failure to arrest the cells at or before mitosis resulted in formation of micronucleated cells, aberrant segregation of chromosomes, microtubule misalignment, and multicentrosomes, leading in eventual mitotic catastrophe cell death. Our observations show that BRCA1 mediates G 2 -M transition mainly through chek1 on 17-allyloamino-17-demethoxy-geldanamycin treatment.

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Section: Discussionsupporting

confidence: 87%

Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in BRCA1-deficient breast cancer cell lines

Zając¹,

Moneo

Carnero

et al. 2008

Molecular Cancer Therapeutics

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“…The patient's clinical course was consistent with primary platinum refractory disease according to standard definitions of platinum sensitivity in patients with ovarian cancer, and her overall survival was only 24 months. Women with BRCA1-associated ovarian cancers are generally thought to have a better survival than those with sporadic ovarian cancer, and BRCA1-deficient tumors generally display increased sensitivity to platinum chemotherapy in vitro (38)(39)(40)(41)(42)(43). It has been difficult to generate cell lines from BRCA1-associated ovarian cancers.…”

Section: Discussionmentioning

confidence: 99%

Functional Characterization of a Novel BRCA1-Null Ovarian Cancer Cell Line in Response to Ionizing Radiation

DelloRusso

Welcsh

Wang

et al. 2007

Molecular Cancer Research

107

110

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The breast and ovarian cancer susceptibility gene BRCA1 plays a major role in the DNA damage response pathway. The lack of well-characterized human BRCA1-null cell lines has limited the investigation of BRCA1 function, particularly with regard to its role in ovarian cancer. We propagated a novel BRCA1-null human ovarian cancer cell line UWB1.289 from a tumor of papillary serous histology, the most common form of ovarian carcinoma. UWB1.289 carries a germline BRCA1 mutation within exon 11 and has a deletion of the wild-type allele. UWB1.289 is estrogen and progesterone receptor negative and has an acquired somatic mutation in p53, similar to the commonly used BRCA1-null breast cancer cell line HCC1937. We used ionizing radiation to induce DNA damage in both UWB1.289 and in a stable UWB1.289 line in which wild-type BRCA1 was restored. We examined several responses to DNA damage in these cell lines, including sensitivity to radiation, cell cycle checkpoint function, and changes in gene expression using microarray analysis. We observed that UWB1.289 is sensitive to ionizing radiation and lacks cell cycle checkpoint functions that are a normal part of the DNA damage response. Restoration of wild-type BRCA1 function in these cells partially restores DNA damage responses. Expression array analysis not only supports this partial functional correction but also reveals interesting new information regarding BRCA1-positive regulation of the expression of claudin 6 and other metastasis-associated genes and negative regulation of multiple IFN-inducible genes. (Mol Cancer Res 2007;5(1):35 -45)

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“…The response to taxanes, in BRCA1 deficient cells is reduced apoptosis conferring resistance (Lafarge et al 2001). The opposite is true for cells with functional BRCA1 (Quinn et al 2003;Tassone et al 2003).…”

Section: Introductionmentioning

confidence: 96%

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

Busschots

O’Toole

O’Leary

et al. 2015

Experimental Cell Research

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211 BRCA1 functions as a differential modulator of chemotherapy induced apoptosis

Cited by 213 publications

References 0 publications

Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in BRCA1-deficient breast cancer cell lines

Mitotic catastrophe cell death induced by heat shock protein 90 inhibitor in BRCA1-deficient breast cancer cell lines

Functional Characterization of a Novel BRCA1-Null Ovarian Cancer Cell Line in Response to Ionizing Radiation

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

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