-
- Nelson E. Brown
- Authors' Affiliations: 1Molecular Oncology Research Institute, Tufts Medical Center; and 2Departments of Radiation Oncology and 3Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts
-
- Rinath Jeselsohn
- Authors' Affiliations: 1Molecular Oncology Research Institute, Tufts Medical Center; and 2Departments of Radiation Oncology and 3Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts
-
- Teeru Bihani
- Authors' Affiliations: 1Molecular Oncology Research Institute, Tufts Medical Center; and 2Departments of Radiation Oncology and 3Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts
-
- Miaofen G. Hu
- Authors' Affiliations: 1Molecular Oncology Research Institute, Tufts Medical Center; and 2Departments of Radiation Oncology and 3Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts
-
- Parthena Foltopoulou
- Authors' Affiliations: 1Molecular Oncology Research Institute, Tufts Medical Center; and 2Departments of Radiation Oncology and 3Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts
-
- Charlotte Kuperwasser
- Authors' Affiliations: 1Molecular Oncology Research Institute, Tufts Medical Center; and 2Departments of Radiation Oncology and 3Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts
-
- Philip W. Hinds
- Authors' Affiliations: 1Molecular Oncology Research Institute, Tufts Medical Center; and 2Departments of Radiation Oncology and 3Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts
書誌事項
- 公開日
- 2012-12-15
- DOI
-
- 10.1158/0008-5472.can-11-4139
- 公開者
- American Association for Cancer Research (AACR)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Overexpression of cyclin D1 is believed to endow mammary epithelial cells (MEC) with a proliferative advantage by virtue of its contribution to pRB inactivation. Accordingly, abrogation of the kinase-dependent function of cyclin D1 is sufficient to render mice resistant to breast cancer initiated by ErbB2. Here, we report that mouse cyclin D1KE/KE MECs (deficient in cyclin D1 activity) upregulate an autophagy-like process but fail to implement ErbB2-induced senescence in vivo. In addition, immortalized cyclin D1KE/KE MECs retain high rates of autophagy and reduced ErbB2-mediated transformation in vitro. However, highlighting its dual role during tumorigenesis, downregulation of autophagy led to an increase in senescence in cyclin D1KE/KE MECs. Autophagy upregulation was also confirmed in human mammary epithelial cells (HMEC) subjected to genetic and pharmacologic inhibition of cyclin D1 activity and, similar to our murine system, simultaneous inhibition of Cdk4/6 and autophagy in HMECs enhanced the senescence response. Collectively, our findings suggest a previously unrecognized function of cyclin D1 in suppressing autophagy in the mammary epithelium. Cancer Res; 72(24); 6477–89. ©2012 AACR.</jats:p>
収録刊行物
-
- Cancer Research
-
Cancer Research 72 (24), 6477-6489, 2012-12-15
American Association for Cancer Research (AACR)
