• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Hepsin 在前列腺癌小鼠模型中与 MYC 协同促进腺癌进展。

Hepsin cooperates with MYC in the progression of adenocarcinoma in a prostate cancer mouse model.

机构信息

Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA.

出版信息

Prostate. 2010 May 1;70(6):591-600. doi: 10.1002/pros.21093.

DOI:10.1002/pros.21093
PMID:19938013
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2925264/
Abstract

BACKGROUND

Hepsin is a cell surface protease that is over-expressed in more than 90% of human prostate cancer cases. The previously developed Probasin-hepsin/Large Probasin-T antigen (PB-hepsin/LPB-Tag) bigenic mouse model of prostate cancer demonstrates that hepsin promotes primary tumors that are a mixture of adenocarcinoma and neuroendocrine (NE) lesions, and metastases that are NE in nature. However, since the majority of human prostate tumors are adenocarcinomas, the contribution of hepsin in the progression of adenocarcinoma requires further investigation.

METHODS

We crossed the PB-hepsin mice with PB-Hi-myc transgenic mouse model of prostate adenocarcinoma and characterized the tumor progression in the resulting PB-hepsin/PB-Hi-myc bigenic mice.

RESULTS

We report that PB-hepsin/PB-Hi-myc bigenic mice develop invasive adenocarcinoma at 4.5 months. Further, histological analysis of the 12- to 17-month-old mice revealed that the PB-hepsin/PB-Hi-myc model develops a higher grade adenocarcinoma compared with age-matched tumors expressing only PB-Hi-myc. Consistent with targeting hepsin to the prostate, the PB-hepsin/PB-Hi-myc tumors showed higher hepsin expression as compared to the age-matched myc tumors. Furthermore, endogenous expression of hepsin increased in the PB-Hi-myc mice as the tumors progressed.

CONCLUSIONS

Although we did not detect any metastases from the prostates in either the PB-hepsin/PB-Hi-myc or the PB-Hi-myc mice, our data suggests that hepsin and myc cooperate during the progression to high-grade prostatic adenocarcinoma.

摘要

背景

Hepsin 是一种细胞表面蛋白酶，在超过 90%的人类前列腺癌病例中过度表达。以前开发的 Probasin-hepsin/Large Probasin-T 抗原（PB-hepsin/LPB-Tag）双基因前列腺癌小鼠模型表明，hepsin 促进了由腺癌和神经内分泌（NE）病变混合组成的原发性肿瘤，并促进了具有 NE 性质的转移。然而，由于大多数人类前列腺肿瘤是腺癌，因此需要进一步研究 hepsin 在腺癌进展中的作用。

方法

我们将 PB-hepsin 小鼠与 PB-Hi-myc 转基因前列腺腺癌小鼠模型杂交，并对由此产生的 PB-hepsin/PB-Hi-myc 双基因小鼠的肿瘤进展进行了特征描述。

结果

我们报告称，PB-hepsin/PB-Hi-myc 双基因小鼠在 4.5 个月时会发展为侵袭性腺癌。此外，对 12-17 个月大的小鼠进行组织学分析表明，与仅表达 PB-Hi-myc 的年龄匹配肿瘤相比，PB-hepsin/PB-Hi-myc 模型发展为更高等级的腺癌。与将 hepsin 靶向前列腺一致，与年龄匹配的 myc 肿瘤相比，PB-hepsin/PB-Hi-myc 肿瘤表现出更高的 hepsin 表达。此外，随着肿瘤的进展，PB-Hi-myc 小鼠中的内源性 hepsin 表达增加。

结论

尽管我们在 PB-hepsin/PB-Hi-myc 或 PB-Hi-myc 小鼠的前列腺中均未检测到任何转移，但我们的数据表明，在向高级别前列腺腺癌进展过程中，hepsin 和 myc 合作。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/4268d0c93dbf/nihms216660f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/fcfc33017c51/nihms216660f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/c206001f99d5/nihms216660f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/77a88f26198c/nihms216660f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/90647d36fd94/nihms216660f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/2f348033e47b/nihms216660f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/4268d0c93dbf/nihms216660f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/fcfc33017c51/nihms216660f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/c206001f99d5/nihms216660f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/77a88f26198c/nihms216660f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/90647d36fd94/nihms216660f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/2f348033e47b/nihms216660f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/489c/2925264/4268d0c93dbf/nihms216660f6.jpg

相似文献

1
Hepsin cooperates with MYC in the progression of adenocarcinoma in a prostate cancer mouse model.Hepsin 在前列腺癌小鼠模型中与 MYC 协同促进腺癌进展。
Prostate. 2010 May 1;70(6):591-600. doi: 10.1002/pros.21093.
2
A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential.一种前列腺素-大T抗原转基因小鼠品系会发展出具有转移潜能的前列腺腺癌和神经内分泌癌。
Cancer Res. 2001 Mar 1;61(5):2239-49.
3
Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer.前列腺素 - 大T抗原转基因小鼠前列腺肿瘤的发生、发展及雄激素依赖性：一种前列腺癌模型
Lab Invest. 1998 Mar;78(3):319-33.
4
MYC cooperates with AKT in prostate tumorigenesis and alters sensitivity to mTOR inhibitors.MYC 与 AKT 在前列腺肿瘤发生中协同作用，并改变对 mTOR 抑制剂的敏感性。
PLoS One. 2011 Mar 4;6(3):e17449. doi: 10.1371/journal.pone.0017449.
5
Development, progression, and androgen-dependence of prostate tumors in probasin-large T antigen transgenic mice: a model for prostate cancer.前列腺素 - 大T抗原转基因小鼠前列腺肿瘤的发生、发展及雄激素依赖性：一种前列腺癌模型
Lab Invest. 1998 Jun;78(6):i-xv.
6
Matrix-dependent regulation of AKT in Hepsin-overexpressing PC3 prostate cancer cells.基质依赖性调节 AKT 在高表达 Hepsin 的 PC3 前列腺癌细胞中的作用。
Neoplasia. 2011 Jul;13(7):579-89. doi: 10.1593/neo.11294.
7
Androgen-dependent prostate epithelial cell selection by targeting ARR(2)PBneo to the LPB-Tag model of prostate cancer.通过将ARR(2)PBneo靶向前列腺癌的LPB-Tag模型来进行雄激素依赖性前列腺上皮细胞选择。
Lab Invest. 2006 Oct;86(10):1074-88. doi: 10.1038/labinvest.3700463. Epub 2006 Aug 7.
8
Hepsin promotes prostate cancer progression and metastasis.肝素酶促进前列腺癌的进展和转移。
Cancer Cell. 2004 Aug;6(2):185-95. doi: 10.1016/j.ccr.2004.07.008.
9
Cooperation between Stat3 and Akt signaling leads to prostate tumor development in transgenic mice.Stat3 和 Akt 信号的相互作用导致转基因小鼠前列腺肿瘤的发展。
Neoplasia. 2011 Mar;13(3):254-65. doi: 10.1593/neo.101388.
10
MYC overexpression induces prostatic intraepithelial neoplasia and loss of Nkx3.1 in mouse luminal epithelial cells.MYC 过表达诱导前列腺上皮内瘤形成和 Nkx3.1 在小鼠腔上皮细胞中的丢失。
PLoS One. 2010 Feb 25;5(2):e9427. doi: 10.1371/journal.pone.0009427.

引用本文的文献

1
Diverse landscape of genetically engineered mouse models: Genomic and molecular insights into prostate cancer.基因工程小鼠模型的多样性：前列腺癌的基因组和分子见解。
Cancer Lett. 2024 Jul 1;593:216954. doi: 10.1016/j.canlet.2024.216954. Epub 2024 May 10.
2
Cooperativity of c-MYC with Krüppel-Like Factor 6 Splice Variant 1 induces phenotypic plasticity and promotes prostate cancer progression and metastasis.c-MYC与Krüppel样因子6剪接变体1的协同作用诱导表型可塑性并促进前列腺癌进展和转移。
bioRxiv. 2024 Feb 1:2024.01.30.577982. doi: 10.1101/2024.01.30.577982.
3
Pre-Clinical Models to Study Human Prostate Cancer.

本文引用的文献

1
Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression.层粘连蛋白-332是组织蛋白酶H的一种底物，组织蛋白酶H是一种与前列腺癌进展相关的蛋白酶。
J Biol Chem. 2008 Nov 7;283(45):30576-84. doi: 10.1074/jbc.M802312200. Epub 2008 Sep 9.
2
Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis.核MYC蛋白过表达是人类前列腺癌发生过程中的早期改变。
Mod Pathol. 2008 Sep;21(9):1156-67. doi: 10.1038/modpathol.2008.111. Epub 2008 Jun 20.
3
Dissociation of epithelial and neuroendocrine carcinoma lineages in the transgenic adenocarcinoma of mouse prostate model of prostate cancer.
用于研究人类前列腺癌的临床前模型
Cancers (Basel). 2023 Aug 22;15(17):4212. doi: 10.3390/cancers15174212.
4
In Vivo Models for Prostate Cancer Research.用于前列腺癌研究的体内模型
Cancers (Basel). 2022 Oct 28;14(21):5321. doi: 10.3390/cancers14215321.
5
Implication of Hepsin from Primary Tumor in the Prognosis of Colorectal Cancer Patients.原发性肿瘤中肝素酶对结直肠癌患者预后的影响。
Cancers (Basel). 2022 Jun 24;14(13):3106. doi: 10.3390/cancers14133106.
6
Clinical Significance of Hepsin and Underlying Signaling Pathways in Prostate Cancer.前列腺癌中赫普辛及相关信号通路的临床意义。
Biomolecules. 2022 Jan 25;12(2):203. doi: 10.3390/biom12020203.
7
Hepsin Promotes Epithelial-Mesenchymal Transition and Cell Invasion Through the miR-222/PPP2R2A/AKT Axis in Prostate Cancer.肝素酶通过miR-222/PPP2R2A/AKT轴促进前列腺癌上皮-间质转化和细胞侵袭。
Onco Targets Ther. 2020 Nov 24;13:12141-12149. doi: 10.2147/OTT.S268025. eCollection 2020.
8
Dysregulation of Type II Transmembrane Serine Proteases and Ligand-Dependent Activation of MET in Urological Cancers.尿路上皮癌中 II 型跨膜丝氨酸蛋白酶的失调和 MET 的配体依赖性激活。
Int J Mol Sci. 2020 Apr 11;21(8):2663. doi: 10.3390/ijms21082663.
9
Neuroendocrine Differentiation of Prostate Cancer-An Intriguing Example of Tumor Evolution at Play.前列腺癌的神经内分泌分化——肿瘤演变的一个有趣实例
Cancers (Basel). 2019 Sep 20;11(10):1405. doi: 10.3390/cancers11101405.
10
Cell surface-anchored serine proteases in cancer progression and metastasis.细胞表面锚定的丝氨酸蛋白酶在癌症进展和转移中的作用。
Cancer Metastasis Rev. 2019 Sep;38(3):357-387. doi: 10.1007/s10555-019-09811-7.
前列腺癌小鼠前列腺转基因腺癌模型中上皮和神经内分泌癌谱系的分离
Am J Pathol. 2008 Jan;172(1):236-46. doi: 10.2353/ajpath.2008.070602. Epub 2007 Dec 21.
4
The roles of proteolytic enzymes in the development of tumour-induced bone disease in breast and prostate cancer.蛋白水解酶在乳腺癌和前列腺癌所致肿瘤性骨病发展过程中的作用。
Bone. 2007 Dec;41(6):912-27. doi: 10.1016/j.bone.2007.07.024. Epub 2007 Aug 22.
5
Mouse models of prostate adenocarcinoma with the capacity to monitor spontaneous carcinogenesis by bioluminescence or fluorescence.具有通过生物发光或荧光监测自发癌变能力的前列腺腺癌小鼠模型。
Cancer Res. 2007 Aug 1;67(15):7525-33. doi: 10.1158/0008-5472.CAN-07-0668.
6
Hepsin and prostate cancer.海普辛与前列腺癌
Front Biosci. 2007 Sep 1;12:5052-9. doi: 10.2741/2447.
7
Antibodies neutralizing hepsin protease activity do not impact cell growth but inhibit invasion of prostate and ovarian tumor cells in culture.中和海普辛蛋白酶活性的抗体不会影响细胞生长，但会抑制培养中的前列腺和卵巢肿瘤细胞的侵袭。
Cancer Res. 2006 Apr 1;66(7):3611-9. doi: 10.1158/0008-5472.CAN-05-2983.
8
Gene expression profiles in prostate cancer: association with patient subgroups and tumour differentiation.前列腺癌中的基因表达谱：与患者亚组及肿瘤分化的关联
Int J Oncol. 2005 Feb;26(2):329-36.
9
Use of multiple biomarkers for a molecular diagnosis of prostate cancer.使用多种生物标志物进行前列腺癌的分子诊断。
Int J Cancer. 2005 May 10;114(6):950-6. doi: 10.1002/ijc.20760.
10
Hepsin promotes prostate cancer progression and metastasis.肝素酶促进前列腺癌的进展和转移。
Cancer Cell. 2004 Aug;6(2):185-95. doi: 10.1016/j.ccr.2004.07.008.