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Cyclin D1 determines mitochondrial function in vivo |
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| Authors: | Sakamaki Toshiyuki Casimiro Mathew C Ju Xiaoming Quong Andrew A Katiyar Sanjay Liu Manran Jiao Xuanmao Li Anping Zhang Xueping Lu Yinan Wang Chenguang Byers Stephen Nicholson Robert Link Todd Shemluck Melvin Yang Jianguo Fricke Stanley T Novikoff Phyllis M Papanikolaou Alexandros Arnold Andrew Albanese Christopher Pestell Richard |
| Affiliation: | Departments of Cancer Biology, Thomas Jefferson University, BLSB, Room 1050, 233 South 10th Street, Philadelphia, PA 19107, USA. |
| Abstract: | The cyclin D1 gene encodes a regulatory subunit of the holoenzyme that phosphorylates and inactivates the pRb tumor suppressor to promote nuclear DNA synthesis. cyclin D1 is overexpressed in human breast cancers and is sufficient for the development of murine mammary tumors. Herein, cyclin D1 is shown to perform a novel function, inhibiting mitochondrial function and size. Mitochondrial activity was enhanced by genetic deletion or antisense or small interfering RNA to cyclin D1. Global gene expression profiling and functional analysis of mammary epithelial cell-targeted cyclin D1 antisense transgenics demonstrated that cyclin D1 inhibits mitochondrial activity and aerobic glycolysis in vivo. Reciprocal regulation of these genes was observed in cyclin D1-induced mammary tumors. Cyclin D1 thus integrates nuclear DNA synthesis and mitochondrial function. |
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