Ovarian cancer as a genetic disease

Lech, Agnieszka; Daneva, Teodora; Pashova, Shina; Gagov, Hristo; Crayton, Robert; Kukwa, Wojciech; Czarnecka, Anna M.; Szczylik, Cezary

doi:10.2741/4119

Cited by 14 publications

(2 citation statements)

References 148 publications

(163 reference statements)

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“…Ovarian cancer is characterized by a high mortality rate among gynecological malignancies worldwide. 1 Accumulating evidence indicates that hereditary factors (e.g., BRCA1) 2 and energy metabolism 3 are implicated in the initiation and progression of ovarian cancer. However, crosstalk between genetic and metabolic mechanisms has not been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

BRCA1 as a nicotinamide adenine dinucleotide (NAD)-dependent metabolic switch in ovarian cancer

Chen

Cao

et al. 2014

Cell Cycle

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Both hereditary factors (e.g., BRCA1) and nicotinamide adenine dinucleotide (NAD)-dependent metabolic pathways are implicated in the initiation and progression of ovarian cancer. However, whether crosstalk exists between BRCA1 and NAD metabolism remains largely unknown. Here, we showed that: (i) BRCA1 inactivation events (mutation and promoter methylation) were accompanied by elevated levels of NAD; (ii) the knockdown or overexpression of BRCA1 was an effective way to induce an increase or decrease of nicotinamide phosphoribosyltransferase (Nampt)-related NAD synthesis, respectively; and (iii) BRCA1 expression patterns were inversely correlated with NAD levels in human ovarian cancer specimens. In addition, it is worth noting that: (i) NAD incubation induced increased levels of BRCA1 in a concentration-dependent manner; (ii) Nampt knockdown-mediated reduction in NAD levels was effective at inhibiting BRCA1 expression; and (iii) the overexpression of Nampt led to higher NAD levels and a subsequent increase in BRCA1 levels in primary ovarian cancer cells and A2780, HO-8910 and ES2 ovarian cancer cell lines. These results highlight a novel link between BRCA1 and NAD. Our findings imply that genetic (e.g., BRCA1 inactivation) and NAD-dependent metabolic pathways are jointly involved in the malignant progression of ovarian cancer.

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Section: Introductionmentioning

confidence: 99%

BRCA1 as a nicotinamide adenine dinucleotide (NAD)-dependent metabolic switch in ovarian cancer

Chen

Cao

et al. 2014

Cell Cycle

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“…Ovarian cancer is characterized by a high mortality rate among the gynecological malignancies worldwide (1). To date, although the exact cause of ovarian cancer remains largely unknown, breast cancer (BRCA) mutations are the only known hereditary factors.…”

Section: Introductionmentioning

confidence: 99%

BRCA1 regulates insulin-like growth factor 1 receptor levels in ovarian cancer

Liu

Guan

2014

Oncology Letters

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Breast cancer 1 (BRCA1) and insulin-like growth factor 1 receptor (IGF1R) are critical in ovarian cancer progression. However, the crosstalk between the BRCA1 and IGF1R signaling pathways in ovarian cancer remains largely unknown. The effects of BRCA1 on IGF1R were assessed in 121 serous ovarian cancer patients (BRCA1 mutation, n=30; non-BRCA1 mutation, n=32; hypermethylated BRCA1 promoter, n=28; and non-methylation, n=31). BRCA1 promoter methylation was analyzed via bisulfite sequencing using primers focused on the core promoter region. The expression levels of BRCA1 and IGF1R were assessed by immunohistochemistry and real-time polymerase chain reaction. Knockdown and overexpression of BRCA1 were achieved using a lentiviral vector in 293T and SKOV3 ovarian cancer cells, and primary non-mutated and BRCA1-mutated ovarian cancer cells. The present study demonstrated that IGF1R expression is increased in non-BRCA1-mutated ovarian cancer when compared with adjacent normal tissue. Furthermore, IGF1R levels are additionally significantly elevated in BRCA1 inactivation ovarian cancer (BRCA1 mutation or hypermethylated BRCA1 promoter). In addition, BRCA1 knockdown was found to be an effective method of activating IGF1R expression in non-BRCA1-mutated ovarian cancer cells. The observations of the current study indicate that BRCA1 may be a potential trigger that is involved in the transcriptional regulation of IGF1R in the development of ovarian cancer.

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MicroRNAs and Clinical Implications in Cancer

Wittmann

2014

MicroRNAs: Key Regulators of Oncogenesis

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Ovarian cancer as a genetic disease

Cited by 14 publications

References 148 publications

BRCA1 as a nicotinamide adenine dinucleotide (NAD)-dependent metabolic switch in ovarian cancer

BRCA1 as a nicotinamide adenine dinucleotide (NAD)-dependent metabolic switch in ovarian cancer

BRCA1 regulates insulin-like growth factor 1 receptor levels in ovarian cancer

MicroRNAs and Clinical Implications in Cancer

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