Open AccessCENP ‐R acts bilaterally as a tumor suppressor and as an oncogene in the two‐stage skin carcinogenesis model
Author(s) -
Okumura Kazuhiro,
Kagawa Naoko,
Saito Megumi,
Yoshizawa Yasuhiro,
Munakata Haruka,
Isogai Eriko,
Fukagawa Tatsuo,
Wakabayashi Yuichi
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13348
Subject(s) - carcinogenesis , biology , dmba , oncogene , cell cycle , mitosis , suppressor , cancer research , cell growth , tumor initiation , cancer , epidermis (zoology) , microbiology and biotechnology , genetics , anatomy
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 DT 40 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.