Modeling the effects of genetic- and diet-induced obesity on melanoma progression in zebrafish.
Modeling the effects of genetic- and diet-induced obesity on melanoma progression in zebrafish.
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DOI：
10.1242/dmm.049671
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发表时间：
2023-01-01
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
肥胖是一个日益严重的问题，与许多癌症的增加有关，通常是以性别特异性的方式。需要临床前模型来解卷积肥胖、性和黑色素瘤之间的交叉。在这里，我们生成了一个斑马鱼系统，可以用作研究这些因素的平台。我们研究了Agrp的种系过表达沿着高脂饮食如何影响依赖于BRAFV 600 E和p53缺失的黑色素瘤。这揭示了在雄性而非雌性肥胖鱼中肿瘤发病率和面积的增加，与临床文献一致。然后，我们确定这是否进一步受到临床相关基因rb 1或ptena/B中额外体细胞突变的影响。我们发现，BRAF;p53; Rb 1产生的肿瘤对黑色素瘤的男性致肥胖作用，而BRAF;p53;Pten则无此作用。这些数据表明，生殖细胞（Agrp）和体细胞（BRAF，Rb 1）突变有助于黑色素瘤中的肥胖相关效应。鉴于斑马鱼中可用的快速遗传工具，这提供了一个高通量系统来剖析肥胖相关癌症中遗传、饮食、性别和宿主因素的相互作用。 肥胖发病率正在上升，导致肥胖相关癌症的发生率增加，通常以性别特异性方式发生。在这里，我们开发了一个斑马鱼模型来研究肥胖，性和黑色素瘤之间的交叉点。
Obesity is a rising concern and associated with an increase in numerous cancers, often in a sex-specific manner. Preclinical models are needed to deconvolute the intersection between obesity, sex and melanoma. Here, we generated a zebrafish system that can be used as a platform for studying these factors. We studied how germline overexpression of Agrp along with a high-fat diet affects melanomas dependent on BRAFV600E and loss of p53. This revealed an increase in tumor incidence and area in male, but not female, obese fish, consistent with the clinical literature. We then determined whether this was further affected by additional somatic mutations in the clinically relevant genes rb1 or ptena/b. We found that the male obesogenic effect on melanoma was present with tumors generated with BRAF;p53;Rb1 but not BRAF;p53;Pten. These data indicate that both germline (Agrp) and somatic (BRAF, Rb1) mutations contribute to obesity-related effects in melanoma. Given the rapid genetic tools available in the zebrafish, this provides a high-throughput system to dissect the interactions of genetics, diet, sex and host factors in obesity-related cancers. Obesity incidence is rising, resulting in increased occurrence of obesity-related cancers often occurring in a sex-specific manner. Here, we developed a zebrafish model to investigate the intersection between obesity, sex and melanoma.
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影响因子：
20.3
作者：
Kautzky-Willer A;Harreiter J;Pacini G
通讯作者：
Pacini G
DOI：
10.5402/2013/680536
发表时间：
2013
期刊：
ISRN preventive medicine
影响因子：
--
作者：
Dobbins M;Decorby K;Choi BC
通讯作者：
Choi BC
影响因子：
4.3
作者：
Callahan SJ;Tepan S;Zhang YM;Lindsay H;Burger A;Campbell NR;Kim IS;Hollmann TJ;Studer L;Mosimann C;White RM
通讯作者：
White RM
影响因子：
2.7
作者：
D'Agati G;Beltre R;Sessa A;Burger A;Zhou Y;Mosimann C;White RM
通讯作者：
White RM
影响因子：
2.9
作者：
Koegler, FH;Schaffhauser, AO;Bray, GA
通讯作者：
Bray, GA