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

Xiaoyun Cheng; Weiya Xia; Jer Yen Yang; Jennifer L. Hsu; Chao Kai Chou; Hui Lung Sun; Shannon L. Wyszomierski; Gordon B. Mills; William J. Muller; Dihua Yu; Mien Chie Hung

doi:10.1016/j.bbrc.2010.10.126

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

Xiaoyun Cheng
, Weiya Xia
, Jer Yen Yang
, Jennifer L. Hsu
, Chao Kai Chou
, Hui Lung Sun
, Shannon L. Wyszomierski
, Gordon B. Mills
, William J. Muller
, Dihua Yu
, Mien Chie Hung

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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.

Original language	English (US)
Pages (from-to)	103-107
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	403
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2010.10.126
State	Published - Dec 3 2010
Externally published	Yes

Funding

This work was supported by grants NIH PO1 CA099031 , NIH CCSG CA16672, DOD COE W81WXH-06-2-2033, The University of Texas MD Anderson Cancer Center/China Medical University and Hospital Sister Institution Fund, Cancer Center Research of Excellence DOH-TD-C-111-005 (Taiwan), The National Breast Cancer Foundation, Inc. and the Patel Memorial Breast Cancer Research Fund.

Funders	Funder number
National Breast Cancer Foundation, Inc.
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	PO1 CA099031, DOD COE W81WXH-06-2-2033
National Institute of Health-National Cancer Institute	P30CA016672
University of Texas M.D. Anderson Cancer Center	DOH-TD-C-111-005

Keywords

Lung metastasis
Mammary tumorigenesis
P21
PKB/Akt

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2010.10.126

Cite this

Cheng, X., Xia, W., Yang, J. Y., Hsu, J. L., Chou, C. K., Sun, H. L., Wyszomierski, S. L., Mills, G. B., Muller, W. J., Yu, D., & Hung, M. C. (2010). Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis. Biochemical and Biophysical Research Communications, 403(1), 103-107. https://doi.org/10.1016/j.bbrc.2010.10.126

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

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.",

keywords = "Lung metastasis, Mammary tumorigenesis, P21, PKB/Akt",

author = "Xiaoyun Cheng and Weiya Xia and Yang, \{Jer Yen\} and Hsu, \{Jennifer L.\} and Chou, \{Chao Kai\} and Sun, \{Hui Lung\} and Wyszomierski, \{Shannon L.\} and Mills, \{Gordon B.\} and Muller, \{William J.\} and Dihua Yu and Hung, \{Mien Chie\}",

note = "Funding Information: This work was supported by grants NIH PO1 CA099031 , NIH CCSG CA16672, DOD COE W81WXH-06-2-2033, The University of Texas MD Anderson Cancer Center/China Medical University and Hospital Sister Institution Fund, Cancer Center Research of Excellence DOH-TD-C-111-005 (Taiwan), The National Breast Cancer Foundation, Inc. and the Patel Memorial Breast Cancer Research Fund.",

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doi = "10.1016/j.bbrc.2010.10.126",

language = "English (US)",

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T1 - Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis

AU - Cheng, Xiaoyun

AU - Xia, Weiya

AU - Yang, Jer Yen

AU - Hsu, Jennifer L.

AU - Chou, Chao Kai

AU - Sun, Hui Lung

AU - Wyszomierski, Shannon L.

AU - Mills, Gordon B.

AU - Muller, William J.

AU - Yu, Dihua

AU - Hung, Mien Chie

N1 - Funding Information: This work was supported by grants NIH PO1 CA099031 , NIH CCSG CA16672, DOD COE W81WXH-06-2-2033, The University of Texas MD Anderson Cancer Center/China Medical University and Hospital Sister Institution Fund, Cancer Center Research of Excellence DOH-TD-C-111-005 (Taiwan), The National Breast Cancer Foundation, Inc. and the Patel Memorial Breast Cancer Research Fund.

PY - 2010/12/3

Y1 - 2010/12/3

N2 - 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.

AB - 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.

KW - Lung metastasis

KW - Mammary tumorigenesis

KW - P21

KW - PKB/Akt

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

Abstract

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Keywords

ASJC Scopus subject areas

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