p21(CIP1/WAF1)在乳腺上皮细胞中的激活加速了乳腺肿瘤的发生，并促进了肺转移。
Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis.
机构信息
Department of Molecular and Cellular Oncology, The University of Texas, M D Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Biochem Biophys Res Commun. 2010 Dec 3;403(1):103-7. doi: 10.1016/j.bbrc.2010.10.126. Epub 2010 Oct 30.
Abstract
While p21 is well known to inhibit cyclin-CDK activity in the nucleus and it has also been demonstrated to have oncogenic properties in different types of human cancers. In vitro studies showed that the oncogenic function of p21is closely related to its cytoplasmic localization. However, it is unclear whether cytoplasmic p21 contributes to tumorigenesis in vivo. To address this question, we generated transgenic mice expressing the Akt-phosphorylated form of p21 (p21T145D) in the mammary epithelium. The results showed that Akt-activated p21 was expressed in the cytoplasm of mammary epithelium. Overexpression of Akt-activated p21 accelerated tumor onset and promoted lung metastasis in MMTV/neu mice, providing evidence that p21, especially cytoplasmic phosphorylated p21, has an oncogenic role in promoting mammary tumorigenesis and metastasis.
摘要
虽然 p21 已被证实可抑制细胞核中环肽依赖性激酶的活性，并且在不同类型的人类癌症中也显示出致癌特性。体外研究表明，p21 的致癌功能与其细胞质定位密切相关。然而，细胞质 p21 是否有助于体内肿瘤发生尚不清楚。为了解决这个问题，我们在乳腺上皮细胞中生成了表达 Akt 磷酸化形式 p21（p21T145D）的转基因小鼠。结果表明，Akt 激活的 p21在乳腺上皮细胞的细胞质中表达。Akt 激活的 p21 的过表达加速了 MMTV/neu 小鼠的肿瘤发生，并促进了肺转移，这为 p21，特别是细胞质磷酸化 p21，在促进乳腺肿瘤发生和转移方面具有致癌作用提供了证据。
相似文献
1
Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis.p21(CIP1/WAF1)在乳腺上皮细胞中的激活加速了乳腺肿瘤的发生，并促进了肺转移。
Biochem Biophys Res Commun. 2010 Dec 3;403(1):103-7. doi: 10.1016/j.bbrc.2010.10.126. Epub 2010 Oct 30.
2
Activation of murine double minute 2 by Akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis.Akt 在乳腺上皮细胞中激活双微体 2 可延缓乳腺退化并加速乳腺肿瘤发生。
Cancer Res. 2010 Oct 1;70(19):7684-9. doi: 10.1158/0008-5472.CAN-09-3231. Epub 2010 Sep 14.
3
Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression.乳腺上皮中Akt（蛋白激酶B）的激活为肿瘤进展提供了关键的细胞存活信号。
Mol Cell Biol. 2001 Mar;21(6):2203-12. doi: 10.1128/MCB.21.6.2203-2212.2001.
4
GPNMB augments Wnt-1 mediated breast tumor initiation and growth by enhancing PI3K/AKT/mTOR pathway signaling and β-catenin activity.GPNMB 通过增强 PI3K/AKT/mTOR 信号通路和 β-连环蛋白活性来增强 Wnt-1 介导的乳腺癌起始和生长。
Oncogene. 2019 Jun;38(26):5294-5307. doi: 10.1038/s41388-019-0793-7. Epub 2019 Mar 26.
5
The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling.受体酪氨酸激酶EphA2通过放大ErbB2信号促进小鼠乳腺腺癌的肿瘤发生和转移进程。
J Clin Invest. 2008 Jan;118(1):64-78. doi: 10.1172/JCI33154.
6
p130Cas as a new regulator of mammary epithelial cell proliferation, survival, and HER2-neu oncogene-dependent breast tumorigenesis.p130Cas作为乳腺上皮细胞增殖、存活及HER2-neu癌基因依赖性乳腺肿瘤发生的新型调节因子。
Cancer Res. 2006 May 1;66(9):4672-80. doi: 10.1158/0008-5472.CAN-05-2909.
7
RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis.RANK 配体介导孕激素诱导的乳腺上皮细胞增殖和癌变。
Nature. 2010 Nov 4;468(7320):103-7. doi: 10.1038/nature09495. Epub 2010 Sep 29.
8
Differential effects of p21(WAF1/CIP1) deficiency on MMTV-ras and MMTV-myc mammary tumor properties.p21（WAF1/CIP1）基因缺失对MMTV-ras和MMTV-myc乳腺肿瘤特性的不同影响。
Cancer Res. 2002 Apr 1;62(7):2077-84.
9
Activation of Akt-1 (PKB-alpha) can accelerate ErbB-2-mediated mammary tumorigenesis but suppresses tumor invasion.Akt-1（蛋白激酶Bα）的激活可加速ErbB-2介导的乳腺肿瘤发生，但会抑制肿瘤侵袭。
Cancer Res. 2004 May 1;64(9):3171-8. doi: 10.1158/0008-5472.can-03-3465.
引用本文的文献
1
Suppression of the long non-coding RNA LINC01279 triggers autophagy and apoptosis in lung cancer by regulating FAK and SIN3A.长链非编码RNA LINC01279的抑制通过调节粘着斑激酶（FAK）和Sin3A相关蛋白（SIN3A）触发肺癌中的自噬和凋亡。
Discov Oncol. 2024 Jan 2;15(1):3. doi: 10.1007/s12672-023-00855-4.
2
Thyroid hormone enhances estrogen-mediated proliferation and cell cycle regulatory pathways in steroid receptor-positive breast Cancer.甲状腺激素增强雌激素介导的类固醇受体阳性乳腺癌中的增殖和细胞周期调节通路。
Cell Cycle. 2023 Sep 18:1-20. doi: 10.1080/15384101.2023.2249702.
3
Sirtuin 4 Inhibits Prostate Cancer Progression and Metastasis by Modulating p21 Nuclear Translocation and Glutamate Dehydrogenase 1 ADP-Ribosylation.沉默调节蛋白4通过调节p21核转位和谷氨酸脱氢酶1的ADP-核糖基化来抑制前列腺癌的进展和转移。
J Oncol. 2022 Jul 7;2022:5498743. doi: 10.1155/2022/5498743. eCollection 2022.
4
The novel roles of virus infection-associated gene CDKN1A in chemoresistance and immune infiltration of glioblastoma.病毒感染相关基因 CDKN1A 在胶质母细胞瘤化疗耐药和免疫浸润中的新作用。
Aging (Albany NY). 2021 Feb 17;13(5):6662-6680. doi: 10.18632/aging.202519.
5
ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients.ROC-1、P21 和 CAIX 作为埃及患者膀胱癌侵袭性的标志物。
Diagn Pathol. 2020 Apr 7;15(1):33. doi: 10.1186/s13000-020-00947-7.
6
The Multifaceted p21 (Cip1/Waf1/) in Cell Differentiation, Migration and Cancer Therapy.细胞分化、迁移及癌症治疗中的多面性p21（Cip1/Waf1/）
Cancers (Basel). 2019 Aug 21;11(9):1220. doi: 10.3390/cancers11091220.
7
Prognostic values of GMPS, PR, CD40, and p21 in ovarian cancer.GMPS、PR、CD40和p21在卵巢癌中的预后价值。
PeerJ. 2019 Jan 25;7:e6301. doi: 10.7717/peerj.6301. eCollection 2019.
8
LincIN, a novel NF90-binding long non-coding RNA, is overexpressed in advanced breast tumors and involved in metastasis.LincIN是一种新型的与NF90结合的长链非编码RNA，在晚期乳腺肿瘤中过度表达并参与转移过程。
Breast Cancer Res. 2017 May 30;19(1):62. doi: 10.1186/s13058-017-0853-2.
9
Expression of CDKN1A/p21 and TGFBR2 in breast cancer and their prognostic significance.CDKN1A/p21和TGFBR2在乳腺癌中的表达及其预后意义。
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14619-29. eCollection 2015.
10
Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy.p21在肝癌发生中的致癌作用提示了一种新的治疗策略。
World J Gastroenterol. 2015 Nov 14;21(42):12150-6. doi: 10.3748/wjg.v21.i42.12150.
本文引用的文献
1
Induction of Akt activity by chemotherapy confers acquired resistance.化疗诱导Akt活性会导致获得性耐药。
J Formos Med Assoc. 2009 Mar;108(3):180-94. doi: 10.1016/S0929-6646(09)60051-6.
2
A new fork for clinical application: targeting forkhead transcription factors in cancer.临床应用的新分支：靶向癌症中的叉头转录因子。
Clin Cancer Res. 2009 Feb 1;15(3):752-7. doi: 10.1158/1078-0432.CCR-08-0124.
3
Somatic cell type specific gene transfer reveals a tumor-promoting function for p21(Waf1/Cip1).体细胞类型特异性基因转移揭示了p21（Waf1/Cip1）的促肿瘤功能。
EMBO J. 2007 Nov 14;26(22):4683-93. doi: 10.1038/sj.emboj.7601886. Epub 2007 Oct 18.
4
Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma.p21Waf1/Cip1在胸腺淋巴瘤中的致瘤活性。
Oncogene. 2006 Jul 6;25(29):4128-32. doi: 10.1038/sj.onc.1209432. Epub 2006 Feb 6.
5
Signaling intricacies take center stage in cancer cells.信号复杂性在癌细胞中占据核心地位。
Cancer Res. 2005 Apr 1;65(7):2511-5. doi: 10.1158/0008-5472.CAN-05-0189.
6
Phosphorylation/cytoplasmic localization of p21Cip1/WAF1 is associated with HER2/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients.p21Cip1/WAF1的磷酸化/细胞质定位与HER2/neu过表达相关，并为乳腺癌患者预后不良提供了一种新的联合预测指标。
Clin Cancer Res. 2004 Jun 1;10(11):3815-24. doi: 10.1158/1078-0432.CCR-03-0527.
7
UCN-01 (7-hydroxystauorsporine) blocks PMA-induced maturation and reciprocally promotes apoptosis in human myelomonocytic leukemia cells (U937).UCN - 01（7 - 羟基星孢菌素）可阻断佛波酯诱导的人骨髓单核细胞白血病细胞（U937）成熟，并相反地促进其凋亡。
Cell Cycle. 2002 Jul-Aug;1(4):273-81. doi: 10.4161/cc.1.4.137.
8
Cell cycle and death control: long live Forkheads.细胞周期与死亡调控：叉头蛋白万岁。
Trends Biochem Sci. 2002 Jul;27(7):352-60. doi: 10.1016/s0968-0004(02)02113-8.
9
Phosphorylation of HDM2 by Akt.Akt对HDM2的磷酸化作用。
Oncogene. 2002 Mar 27;21(13):1955-62. doi: 10.1038/sj.onc.1205276.
10
Oncogenic functions of tumour suppressor p21(Waf1/Cip1/Sdi1): association with cell senescence and tumour-promoting activities of stromal fibroblasts.肿瘤抑制因子p21（Waf1/Cip1/Sdi1）的致癌功能：与细胞衰老及基质成纤维细胞的促肿瘤活性相关
Cancer Lett. 2002 May 8;179(1):1-14. doi: 10.1016/s0304-3835(01)00847-3.
Zotero 插件