CENP-R acts bilaterally as a tumor suppressor and as an oncogene in the two-stage skin carcinogenesis model.

Kazuhiro Okumura, Naoko Kagawa, Megumi Saito, Yasuhiro Yoshizawa, Haruka Munakata, Eriko Isogai, Tatsuo Fukagawa, Yuichi Wakabayashi

Cancer science 2017 Nov

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CENP-R is a component of the CENP-O complex, including CENP-O, CENP-P, CENP-Q, CENP-R, and CENP-U and is constitutively localized to kinetochores throughout the cell cycle in vertebrates. CENP-R-deficient chicken DT40 cells are viable and show a very minor effect on mitosis. To investigate the functional roles of CENP-R in vivo, we generated CENP-R-deficient mice (Cenp-r-/- ). Mice heterozygous or homozygous for Cenp-r null mutation are viable and healthy, with no apparent defect in growth and morphology, indicating Cenp-r is not essential for normal development. Accordingly, to investigate the role of the Cenp-r gene in skin carcinogenesis, we subjected Cenp-r-/- mice to the 7,12-dimethylbenz(a)anthracene (DMBA)/TPA chemical carcinogenesis protocol and monitored tumor development. As a result, Cenp-r-/- mice initially developed significantly more papillomas than control wild-type mice. However, papillomas in Cenp-r-/- mice showed a decrease of proliferative cells and an increase of apoptotic cells. As a result, they did not grow bigger and some papillomas showed substantial regression. Furthermore, papillomas in Cenp-r-/- mice showed lower frequency of malignant conversion to squamous cell carcinomas. These results indicate Cenp-r functions bilaterally in cancer development: during early developmental stages, Cenp-r functions as a tumor suppressor, but during the expansion and progression of papillomas it functions as a tumor-promoting factor. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Citation

Kazuhiro Okumura, Naoko Kagawa, Megumi Saito, Yasuhiro Yoshizawa, Haruka Munakata, Eriko Isogai, Tatsuo Fukagawa, Yuichi Wakabayashi. CENP-R acts bilaterally as a tumor suppressor and as an oncogene in the two-stage skin carcinogenesis model. Cancer science. 2017 Nov;108(11):2142-2148