Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis

► Akt-activated p21 was primarily expressed in cytoplasm of cells in transgenic mice. ► Akt-activated p21 accelerated tumor onset in MMTV/neu mice. ► Akt-activated p21 promoted lung metastasis in MMTV/neu mice. ► In vivo evidence that cytoplasmic p21 functions as an oncogene. While p21 is well known...

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Published in	Biochemical and biophysical research communications Vol. 403; no. 1; pp. 103 - 107
Main Authors	Cheng, Xiaoyun, Xia, Weiya, Yang, Jer-Yen, Hsu, Jennifer L., Chou, Chao-Kai, Sun, Hui-Lung, Wyszomierski, Shannon L., Mills, Gordon B., Muller, William J., Yu, Dihua, Hung, Mien-Chie
Format	Journal Article
Language	English
Published	United States Elsevier Inc 03.12.2010
Subjects	Animals Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Cyclin-Dependent Kinase Inhibitor p21 - biosynthesis Epithelium - metabolism Epithelium - pathology Female Humans Lung metastasis Lung Neoplasms - metabolism Lung Neoplasms - secondary Mammary Neoplasms, Experimental - metabolism Mammary Neoplasms, Experimental - pathology Mammary tumorigenesis Mice Mice, Transgenic Mouse mammary tumor virus p21 PKB/Akt Proto-Oncogene Proteins c-akt - metabolism p21
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Abstract	► Akt-activated p21 was primarily expressed in cytoplasm of cells in transgenic mice. ► Akt-activated p21 accelerated tumor onset in MMTV/neu mice. ► Akt-activated p21 promoted lung metastasis in MMTV/neu mice. ► In vivo evidence that cytoplasmic p21 functions as an oncogene. 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.
AbstractList	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. ► Akt-activated p21 was primarily expressed in cytoplasm of cells in transgenic mice. ► Akt-activated p21 accelerated tumor onset in MMTV/neu mice. ► Akt-activated p21 promoted lung metastasis in MMTV/neu mice. ► In vivo evidence that cytoplasmic p21 functions as an oncogene. 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. 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.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. a-[ordm Akt-activated p21 was primarily expressed in cytoplasm of cells in transgenic mice. a-[ordm Akt-activated p21 accelerated tumor onset in MMTV/neu mice. a-[ordm Akt-activated p21 promoted lung metastasis in MMTV/neu mice. a-[ordm In vivo evidence that cytoplasmic p21 functions as an oncogene. 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. 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.
Author	Hsu, Jennifer L. Hung, Mien-Chie Cheng, Xiaoyun Sun, Hui-Lung Xia, Weiya Chou, Chao-Kai Muller, William J. Wyszomierski, Shannon L. Yang, Jer-Yen Mills, Gordon B. Yu, Dihua
AuthorAffiliation	2 Departments of System Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA 5 Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical and University Hospital, Taichung 404, Taiwan 1 Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA 4 Department of Medicine and Biochemistry, McGill University, Montreal, Quebec, H3A1A1, Canada 3 Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas 77030, USA
AuthorAffiliation_xml	– name: 1 Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA – name: 5 Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical and University Hospital, Taichung 404, Taiwan – name: 4 Department of Medicine and Biochemistry, McGill University, Montreal, Quebec, H3A1A1, Canada – name: 2 Departments of System Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA – name: 3 Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas 77030, USA
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Cites_doi	10.1038/35060032 10.1158/1078-0432.CCR-08-0124 10.1006/excr.1994.1063 10.1038/sj.emboj.7601886 10.1016/S0960-9822(99)80265-6 10.1038/sj.cdd.4400706 10.1016/0092-8674(94)90379-4 10.1158/1078-0432.CCR-03-0527 10.1038/sj.onc.1205276 10.1073/pnas.181181198 10.1074/jbc.M109062200 10.4161/cc.1.4.138 10.1158/0008-5472.CAN-05-0189 10.1038/ncb1101-973 10.1038/sj.onc.1202148 10.1128/MCB.21.6.2203-2212.2001 10.1128/MCB.19.5.3842 10.1016/0092-8674(88)90184-5 10.1038/35060148 10.1016/S0092-8674(00)80405-5 10.1073/pnas.94.26.14590 10.1016/S0968-0004(02)02113-8 10.1038/366707a0 10.1016/S0304-3835(01)00847-3 10.1093/emboj/18.5.1223 10.1016/S0929-6646(09)60051-6 10.1038/sj.onc.1209432
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References	Hutchinson, Jin, Cardiff, Woodgett, Muller (b0015) 2001; 21 Zhou, Liao, Xia, Spohn, Lee, Hung (b0055) 2001; 3 Suzuki, Kawano, Hayashida, Hayasaki, Tsutomi, Akahane (b0085) 2000; 7 Kane, Shapiro, Stokoe, Weiss (b0020) 1999; 9 Rahmani, Grant (b0105) 2002; 1 Dulic, Kaufmann, Wilson, Tlsty, Lees, Harper, Elledge, Reed (b0070) 1994; 76 Kumar, Hung (b0010) 2005; 65 Suzuki, Tsutomi, Yamamoto, Shibutani, Akahane (b0080) 1999; 19 Mayo, Donner (b0045) 2001; 98 Datta, Dudek, Tao, Masters, Fu, Gotoh, Greenberg (b0025) 1997; 91 Ashcroft, Ludwig, Woods, Copeland, Weber, MacRae, Vousden (b0040) 2002; 21 Burgering, Kops (b0030) 2002; 27 Li, Dowbenko, Lasky (b0095) 2002; 277 Muller, Sinn, Pattengale, Wallace, Leder (b0120) 1988; 54 De la Cueva, Garcia-Cao, Herranz, Lopez, Garcia-Palencia, Flores, Serrano, Fernandez-Piqueras, Martin-Caballero (b0125) 2006; 25 Xia, Chen, Zhou, Sun, Lee, Liao, Zhou, Hung (b0110) 2004; 10 Noda, Ning, Venable, Pereira-Smith, Smith (b0065) 1994; 211 Liu, Yeh, Zhu, Leversha, Cordon-Cardo, Ghossein, Singh, Holland, Koff (b0135) 2007; 26 Zhou, Liao, Xia, Zou, Spohn, Hung (b0050) 2001; 3 Roninson (b0075) 2002; 179 Huang, Hung (b0005) 2009; 108 Gu, Turck, Morgan (b0060) 1993; 366 El-Deiry (b0100) 2001; 3 Yang, Hung (b0035) 2009; 15 Deng, Xia, Hung (b0115) 1998; 17 Wang, Elson, Leder (b0130) 1997; 94 Asada, Yamada, Ichijo, Delia, Miyazono, Fukumuro, Mizutani (b0090) 1999; 18 Kane (10.1016/j.bbrc.2010.10.126_b0020) 1999; 9 Hutchinson (10.1016/j.bbrc.2010.10.126_b0015) 2001; 21 Suzuki (10.1016/j.bbrc.2010.10.126_b0080) 1999; 19 Gu (10.1016/j.bbrc.2010.10.126_b0060) 1993; 366 Deng (10.1016/j.bbrc.2010.10.126_b0115) 1998; 17 Liu (10.1016/j.bbrc.2010.10.126_b0135) 2007; 26 Datta (10.1016/j.bbrc.2010.10.126_b0025) 1997; 91 Mayo (10.1016/j.bbrc.2010.10.126_b0045) 2001; 98 De la Cueva (10.1016/j.bbrc.2010.10.126_b0125) 2006; 25 Zhou (10.1016/j.bbrc.2010.10.126_b0055) 2001; 3 Muller (10.1016/j.bbrc.2010.10.126_b0120) 1988; 54 Zhou (10.1016/j.bbrc.2010.10.126_b0050) 2001; 3 Noda (10.1016/j.bbrc.2010.10.126_b0065) 1994; 211 Wang (10.1016/j.bbrc.2010.10.126_b0130) 1997; 94 Burgering (10.1016/j.bbrc.2010.10.126_b0030) 2002; 27 Rahmani (10.1016/j.bbrc.2010.10.126_b0105) 2002; 1 Suzuki (10.1016/j.bbrc.2010.10.126_b0085) 2000; 7 Xia (10.1016/j.bbrc.2010.10.126_b0110) 2004; 10 Huang (10.1016/j.bbrc.2010.10.126_b0005) 2009; 108 Roninson (10.1016/j.bbrc.2010.10.126_b0075) 2002; 179 Li (10.1016/j.bbrc.2010.10.126_b0095) 2002; 277 Asada (10.1016/j.bbrc.2010.10.126_b0090) 1999; 18 El-Deiry (10.1016/j.bbrc.2010.10.126_b0100) 2001; 3 Ashcroft (10.1016/j.bbrc.2010.10.126_b0040) 2002; 21 Dulic (10.1016/j.bbrc.2010.10.126_b0070) 1994; 76 Yang (10.1016/j.bbrc.2010.10.126_b0035) 2009; 15 Kumar (10.1016/j.bbrc.2010.10.126_b0010) 2005; 65
References_xml	– volume: 7 start-page: 721 year: 2000 end-page: 728 ident: b0085 article-title: Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A publication-title: Cell Death Differ. – volume: 211 start-page: 90 year: 1994 end-page: 98 ident: b0065 article-title: Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen publication-title: Exp. Cell Res. – volume: 3 start-page: E71 year: 2001 end-page: E73 ident: b0100 article-title: Akt takes centre stage in cell-cycle deregulation publication-title: Nat. Cell Biol. – volume: 94 start-page: 14590 year: 1997 end-page: 14595 ident: b0130 article-title: Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice publication-title: Proc. Natl. Acad. Sci. USA – volume: 27 start-page: 352 year: 2002 end-page: 360 ident: b0030 article-title: Cell cycle and death control: long live Forkheads publication-title: Trends Biochem. Sci. – volume: 76 start-page: 1013 year: 1994 end-page: 1023 ident: b0070 article-title: p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest publication-title: Cell – volume: 17 start-page: 2167 year: 1998 end-page: 2175 ident: b0115 article-title: Adenovirus 5 E1A-mediated tumor suppression associated with E1A-mediated apoptosis in vivo publication-title: Oncogene – volume: 179 start-page: 1 year: 2002 end-page: 14 ident: b0075 article-title: Oncogenic functions of tumour suppressor p21(Waf1/Cip1/Sdi1): association with cell senescence and tumour-promoting activities of stromal fibroblasts publication-title: Cancer Lett. – volume: 3 start-page: 973 year: 2001 end-page: 982 ident: b0050 article-title: HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation publication-title: Nat. Cell Biol. – volume: 65 start-page: 2511 year: 2005 end-page: 2515 ident: b0010 article-title: Signaling intricacies take center stage in cancer cells publication-title: Cancer Res. – volume: 98 start-page: 11598 year: 2001 end-page: 11603 ident: b0045 article-title: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus publication-title: Proc. Natl. Acad. Sci. USA – volume: 18 start-page: 1223 year: 1999 end-page: 1234 ident: b0090 article-title: Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation publication-title: EMBO J. – volume: 25 start-page: 4128 year: 2006 end-page: 4132 ident: b0125 article-title: Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma publication-title: Oncogene – volume: 3 start-page: 245 year: 2001 end-page: 252 ident: b0055 article-title: Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells publication-title: Nat. Cell Biol. – volume: 1 start-page: 273 year: 2002 end-page: 281 ident: b0105 article-title: UCN-01 (7-hydroxystauorsporine) blocks PMA-induced maturation and reciprocally promotes apoptosis in human myelomonocytic leukemia cells (U937) publication-title: Cell Cycle – volume: 366 start-page: 707 year: 1993 end-page: 710 ident: b0060 article-title: Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit publication-title: Nature – volume: 15 start-page: 752 year: 2009 end-page: 757 ident: b0035 article-title: A new fork for clinical application: targeting forkhead transcription factors in cancer publication-title: Clin. Cancer Res. – volume: 21 start-page: 1955 year: 2002 end-page: 1962 ident: b0040 article-title: Phosphorylation of HDM2 by Akt publication-title: Oncogene – volume: 91 start-page: 231 year: 1997 end-page: 241 ident: b0025 article-title: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery publication-title: Cell – volume: 10 start-page: 3815 year: 2004 end-page: 3824 ident: b0110 article-title: 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 publication-title: Clin. Cancer Res. – volume: 9 start-page: 601 year: 1999 end-page: 604 ident: b0020 article-title: Induction of NF-kappaB by the Akt/PKB kinase publication-title: Curr. Biol. – volume: 54 start-page: 105 year: 1988 end-page: 115 ident: b0120 article-title: Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene publication-title: Cell – volume: 19 start-page: 3842 year: 1999 end-page: 3847 ident: b0080 article-title: Mitochondrial regulation of cell death: mitochondria are essential for procaspase 3-p21 complex formation to resist Fas-mediated cell death publication-title: Mol. Cell. Biol. – volume: 21 start-page: 2203 year: 2001 end-page: 2212 ident: b0015 article-title: Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression publication-title: Mol. Cell. Biol. – volume: 26 start-page: 4683 year: 2007 end-page: 4693 ident: b0135 article-title: Somatic cell type specific gene transfer reveals a tumor-promoting function for p21(Waf1/Cip1) publication-title: EMBO J. – volume: 108 start-page: 180 year: 2009 end-page: 194 ident: b0005 article-title: Induction of Akt activity by chemotherapy confers acquired resistance publication-title: J. Formos. Med. Assoc. – volume: 277 start-page: 11352 year: 2002 end-page: 11361 ident: b0095 article-title: AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival publication-title: J. Biol. Chem. – volume: 3 start-page: 245 year: 2001 ident: 10.1016/j.bbrc.2010.10.126_b0055 article-title: Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells publication-title: Nat. Cell Biol. doi: 10.1038/35060032 – volume: 15 start-page: 752 year: 2009 ident: 10.1016/j.bbrc.2010.10.126_b0035 article-title: A new fork for clinical application: targeting forkhead transcription factors in cancer publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-08-0124 – volume: 211 start-page: 90 year: 1994 ident: 10.1016/j.bbrc.2010.10.126_b0065 article-title: Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen publication-title: Exp. Cell Res. doi: 10.1006/excr.1994.1063 – volume: 26 start-page: 4683 year: 2007 ident: 10.1016/j.bbrc.2010.10.126_b0135 article-title: Somatic cell type specific gene transfer reveals a tumor-promoting function for p21(Waf1/Cip1) publication-title: EMBO J. doi: 10.1038/sj.emboj.7601886 – volume: 9 start-page: 601 year: 1999 ident: 10.1016/j.bbrc.2010.10.126_b0020 article-title: Induction of NF-kappaB by the Akt/PKB kinase publication-title: Curr. Biol. doi: 10.1016/S0960-9822(99)80265-6 – volume: 7 start-page: 721 year: 2000 ident: 10.1016/j.bbrc.2010.10.126_b0085 article-title: Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A publication-title: Cell Death Differ. doi: 10.1038/sj.cdd.4400706 – volume: 76 start-page: 1013 year: 1994 ident: 10.1016/j.bbrc.2010.10.126_b0070 article-title: p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest publication-title: Cell doi: 10.1016/0092-8674(94)90379-4 – volume: 10 start-page: 3815 year: 2004 ident: 10.1016/j.bbrc.2010.10.126_b0110 article-title: 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 publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-03-0527 – volume: 21 start-page: 1955 year: 2002 ident: 10.1016/j.bbrc.2010.10.126_b0040 article-title: Phosphorylation of HDM2 by Akt publication-title: Oncogene doi: 10.1038/sj.onc.1205276 – volume: 98 start-page: 11598 year: 2001 ident: 10.1016/j.bbrc.2010.10.126_b0045 article-title: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.181181198 – volume: 277 start-page: 11352 year: 2002 ident: 10.1016/j.bbrc.2010.10.126_b0095 article-title: AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival publication-title: J. Biol. Chem. doi: 10.1074/jbc.M109062200 – volume: 1 start-page: 273 year: 2002 ident: 10.1016/j.bbrc.2010.10.126_b0105 article-title: UCN-01 (7-hydroxystauorsporine) blocks PMA-induced maturation and reciprocally promotes apoptosis in human myelomonocytic leukemia cells (U937) publication-title: Cell Cycle doi: 10.4161/cc.1.4.138 – volume: 65 start-page: 2511 year: 2005 ident: 10.1016/j.bbrc.2010.10.126_b0010 article-title: Signaling intricacies take center stage in cancer cells publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-05-0189 – volume: 3 start-page: 973 year: 2001 ident: 10.1016/j.bbrc.2010.10.126_b0050 article-title: HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation publication-title: Nat. Cell Biol. doi: 10.1038/ncb1101-973 – volume: 17 start-page: 2167 year: 1998 ident: 10.1016/j.bbrc.2010.10.126_b0115 article-title: Adenovirus 5 E1A-mediated tumor suppression associated with E1A-mediated apoptosis in vivo publication-title: Oncogene doi: 10.1038/sj.onc.1202148 – volume: 21 start-page: 2203 year: 2001 ident: 10.1016/j.bbrc.2010.10.126_b0015 article-title: Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.21.6.2203-2212.2001 – volume: 19 start-page: 3842 year: 1999 ident: 10.1016/j.bbrc.2010.10.126_b0080 article-title: Mitochondrial regulation of cell death: mitochondria are essential for procaspase 3-p21 complex formation to resist Fas-mediated cell death publication-title: Mol. Cell. Biol. doi: 10.1128/MCB.19.5.3842 – volume: 54 start-page: 105 year: 1988 ident: 10.1016/j.bbrc.2010.10.126_b0120 article-title: Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene publication-title: Cell doi: 10.1016/0092-8674(88)90184-5 – volume: 3 start-page: E71 year: 2001 ident: 10.1016/j.bbrc.2010.10.126_b0100 article-title: Akt takes centre stage in cell-cycle deregulation publication-title: Nat. Cell Biol. doi: 10.1038/35060148 – volume: 91 start-page: 231 year: 1997 ident: 10.1016/j.bbrc.2010.10.126_b0025 article-title: Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery publication-title: Cell doi: 10.1016/S0092-8674(00)80405-5 – volume: 94 start-page: 14590 year: 1997 ident: 10.1016/j.bbrc.2010.10.126_b0130 article-title: Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.94.26.14590 – volume: 27 start-page: 352 year: 2002 ident: 10.1016/j.bbrc.2010.10.126_b0030 article-title: Cell cycle and death control: long live Forkheads publication-title: Trends Biochem. Sci. doi: 10.1016/S0968-0004(02)02113-8 – volume: 366 start-page: 707 year: 1993 ident: 10.1016/j.bbrc.2010.10.126_b0060 article-title: Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit publication-title: Nature doi: 10.1038/366707a0 – volume: 179 start-page: 1 year: 2002 ident: 10.1016/j.bbrc.2010.10.126_b0075 article-title: Oncogenic functions of tumour suppressor p21(Waf1/Cip1/Sdi1): association with cell senescence and tumour-promoting activities of stromal fibroblasts publication-title: Cancer Lett. doi: 10.1016/S0304-3835(01)00847-3 – volume: 18 start-page: 1223 year: 1999 ident: 10.1016/j.bbrc.2010.10.126_b0090 article-title: Apoptosis inhibitory activity of cytoplasmic p21(Cip1/WAF1) in monocytic differentiation publication-title: EMBO J. doi: 10.1093/emboj/18.5.1223 – volume: 108 start-page: 180 year: 2009 ident: 10.1016/j.bbrc.2010.10.126_b0005 article-title: Induction of Akt activity by chemotherapy confers acquired resistance publication-title: J. Formos. Med. Assoc. doi: 10.1016/S0929-6646(09)60051-6 – volume: 25 start-page: 4128 year: 2006 ident: 10.1016/j.bbrc.2010.10.126_b0125 article-title: Tumorigenic activity of p21Waf1/Cip1 in thymic lymphoma publication-title: Oncogene doi: 10.1038/sj.onc.1209432
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Snippet	► Akt-activated p21 was primarily expressed in cytoplasm of cells in transgenic mice. ► Akt-activated p21 accelerated tumor onset in MMTV/neu mice. ►... 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... a-[ordm Akt-activated p21 was primarily expressed in cytoplasm of cells in transgenic mice. a-[ordm Akt-activated p21 accelerated tumor onset in MMTV/neu mice....
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SubjectTerms	Animals Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Cyclin-Dependent Kinase Inhibitor p21 - biosynthesis Epithelium - metabolism Epithelium - pathology Female Humans Lung metastasis Lung Neoplasms - metabolism Lung Neoplasms - secondary Mammary Neoplasms, Experimental - metabolism Mammary Neoplasms, Experimental - pathology Mammary tumorigenesis Mice Mice, Transgenic Mouse mammary tumor virus p21 PKB/Akt Proto-Oncogene Proteins c-akt - metabolism
Title	Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis
URI	https://dx.doi.org/10.1016/j.bbrc.2010.10.126 https://www.ncbi.nlm.nih.gov/pubmed/21040707 https://www.proquest.com/docview/816386026 https://www.proquest.com/docview/907155268 https://pubmed.ncbi.nlm.nih.gov/PMC3001223
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