Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

被引：15

作者：

Cimmino, Flora ^{[1
,2
]}

Avitabile, Marianna ^{[1
,2
]}

Lasorsa, Vito Alessandro ^{[1
,2
]}

Pezone, Lucia ^{[1
]}

Cardinale, Antonella ^{[1
]}

Montella, Annalaura ^{[2
]}

Cantalupo, Sueva ^{[3
]}

Iolascon, Achille ^{[1
,2
]}

Capasso, Mario ^{[1
,2
,3
]}

机构：

[1] Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, Naples, Italy

[2] CEINGE Biotecnol Avanzate, Naples, Italy

[3] IRCCS SDN, Naples, Italy

来源：

JOURNAL OF CANCER | 2020年 / 11卷 / 06期

关键词：

Neuroblastoma; BARD1; tumor suppressor gene; DNA-DAMAGE RESPONSE; FAMILIAL NEUROBLASTOMA; GENETIC PREDISPOSITION; BRCA1; EXPRESSION; SUSCEPTIBILITY; CANCER; P53; PHOSPHORYLATION; IDENTIFICATION;

D O I：

10.7150/jca.36164

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BARD1 is associated with the development of high-risk neuroblastoma patients. Particularly, the expression of full length (FL) isoform, FL BARD1, correlates to high-risk neuroblastoma development and its inhibition is sufficient to induce neuroblastoma cells towards a worst phenotype. Here we have investigated the mechanisms of FL BARD1 in neuroblastoma cell lines depleted for FL BARD1 expression. We have shown that FL BARD1 expression protects the cells from spontaneous DNA damage and from damage accumulated after irradiation. We demonstrated a role for FL BARD1 as tumor suppressor to prevent unscheduled mitotic entry of DNA damaged cells and to lead to death cells that have bypassed cell cycle checkpoints. FL BARD1-depleted cells that have survived to checkpoints acquire features of aggressiveness. Overall, our results show that FL BARD1 may defend cells against cancer and prevent malignant transformation of cells.

引用

页码：1495 / 1504

页数：10

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