The Relationship between Leptin, the Leptin Receptor and FGFR1 in Primary Human Breast Tumors.
The Relationship between Leptin, the Leptin Receptor and FGFR1 in Primary Human Breast Tumors.
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DOI：
10.3390/cells9102224
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发表时间：
2020-10-01
期刊：
影响因子：
6
通讯作者：
Bernard JJ
中科院分区：
文献类型：
--
作者：
Boothby-Shoemaker W;Benham V;Paithankar S;Shankar R;Chen B;Bernard JJ
肥胖与乳腺癌风险增加和癌症预后不良有关;然而，这些观察结果的确切病因尚未完全确定。我们之前的研究表明，脂肪组织来源的成纤维细胞生长因子-2（FGF 2）通过激活成纤维细胞生长因子受体-1（FGFR 1）促进上皮细胞的恶性转化。FGF 2在肥胖的情况下增加，并且增加的血清水平与内分泌抵抗性乳腺癌相关。瘦素是肥胖的标志物，并通过多种机制促进乳腺癌的发生。在这项研究中，我们利用公共基因表达数据集来评估乳腺癌中FGFR 1，瘦素和瘦素受体（LepR）之间的关联。我们发现在原发性乳腺肿瘤中FGFR 1和瘦素蛋白拷贝数之间存在正相关。这些观察结果与Janus激酶2（Jak 2）mRNA与瘦素受体（LepR）mRNA和FGFR 1 mRNA之间的正相关性一致。此外，两种单独的Jak 2抑制剂减弱瘦素+FGF 2刺激和小鼠脂肪组织刺激的MCF-10A转化。这些结果表明，肥胖患者血清FGF 2和瘦素升高如何通过Jak 2信号传导促进表达升高的FGFR 1和LepR的肿瘤的癌症进展。因此，Jak 2是FGFR 1扩增乳腺癌的潜在治疗靶点，特别是在肥胖症的背景下。
Obesity is associated with increased breast cancer risk and poorer cancer outcomes; however, the precise etiology of these observations has not been fully identified. Our previous research suggests that adipose tissue-derived fibroblast growth factor-2 (FGF2) promotes the malignant transformation of epithelial cells through the activation of fibroblast growth factor receptor-1 (FGFR1). FGF2 is increased in the context of obesity, and increased sera levels have been associated with endocrine-resistant breast cancer. Leptin is a marker of obesity and promotes breast carcinogenesis through several mechanisms. In this study, we leverage public gene expression datasets to evaluate the associations between FGFR1, leptin, and the leptin receptor (LepR) in breast cancer. We show a positive association between FGFR1 and leptin protein copy number in primary breast tumors. These observations coincided with a positive association between Janus kinase 2 (Jak2) mRNA with both leptin receptor (LepR) mRNA and FGFR1 mRNA. Moreover, two separate Jak2 inhibitors attenuated both leptin+FGF2-stimulated and mouse adipose tissue-stimulated MCF-10A transformation. These results demonstrate how elevated sera FGF2 and leptin in obese patients may promote cancer progression in tumors that express elevated FGFR1 and LepR through Jak2 signaling. Therefore, Jak2 is a potential therapeutic target for FGFR1 amplified breast cancer, especially in the context of obesity.
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影响因子：
4.8
作者：
Gonzalez-Perez RR;Xu Y;Guo S;Watters A;Zhou W;Leibovich SJ
通讯作者：
Leibovich SJ
DOI：
10.1080/01635581.2020.1792946
发表时间：
2020-07-22
影响因子：
2.9
作者：
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11.2
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影响因子：
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通讯作者：
Anderson, Garnet L.
影响因子：
7.7
作者：
Chan, JL;Blüher, S;Mantzoros, CS
通讯作者：
Mantzoros, CS