Methylation and expression of p16INK4 tumor suppressor gene in primary colorectal cancer tissues

  • Authors:
    • Byung No Kim
    • Hirofumi Yamamoto
    • Kimimasa Ikeda
    • Bazarragchaa Damdinsuren
    • Yurika Sugita
    • Chew Yee Ngan
    • Yujiro Fujie
    • Minoru Ogawa
    • Taishi Hata
    • Masataka Ikeda
    • Masayuki Ohue
    • Mitsugu Sekimoto
    • Takushi Monden
    • Nariaki Matsuura
    • Morito Monden
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/ijo.26.5.1217
  • Pages: 1217-1226
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It is known that p16INK4 tumor suppressor gene expression in colon cancer cells is repressed by methylation at the CpG island of promoter, but in vivo silencing of p16 gene is not fully understood. Some studies showed that primary colorectal cancer (CRC) tissues often overexpress the p16 protein, while others showed the high incidence of p16 methylation. The aim of this study was to clarify p16 gene regulation in vivo. We used real-time methylation-specific PCR (MSP) to examine density of p16 methylation, and immunohistochemistry, Western blot analysis to determine p16 protein expression. Methylation was detected in 5 CRC cell lines tested and 9 of 21 (42.9%) CRCs. Four of 5 CRC cell lines did not express p16 mRNA, but 6 of 9 CRCs did express p16 mRNA even with methylation. Real-time MSP showed that CRC tissues had a wide variety in methylation density (methylation index: 0.28-0.91) and that highly methylated CRC tissues displayed significantly lower p16 mRNA expression than those with no-methylation or low-methylation. Immunohistochemistry showed that the majority of CRCs (53 of 55: 96.4%) overexpressed the p16 protein. Low p16 expression was associated with lymph node metastasis (p=0.003) and large tumor size (p=0.048). Western blot in a subset of non-tumor and tumor samples showed a consistent overexpression of the p16 protein. These results showed that CRC tissues displayed variable methylation density, which may be characteristics of p16 gene methylation in vivo. Our data suggest that a low p16 expression due to methylation may contribute to tumor enlargement and expansion of CRC.

Related Articles

Journal Cover

May 2005
Volume 26 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kim BN, Yamamoto H, Ikeda K, Damdinsuren B, Sugita Y, Ngan CY, Fujie Y, Ogawa M, Hata T, Ikeda M, Ikeda M, et al: Methylation and expression of p16INK4 tumor suppressor gene in primary colorectal cancer tissues. Int J Oncol 26: 1217-1226, 2005.
APA
Kim, B.N., Yamamoto, H., Ikeda, K., Damdinsuren, B., Sugita, Y., Ngan, C.Y. ... Monden, M. (2005). Methylation and expression of p16INK4 tumor suppressor gene in primary colorectal cancer tissues. International Journal of Oncology, 26, 1217-1226. https://doi.org/10.3892/ijo.26.5.1217
MLA
Kim, B. N., Yamamoto, H., Ikeda, K., Damdinsuren, B., Sugita, Y., Ngan, C. Y., Fujie, Y., Ogawa, M., Hata, T., Ikeda, M., Ohue, M., Sekimoto, M., Monden, T., Matsuura, N., Monden, M."Methylation and expression of p16INK4 tumor suppressor gene in primary colorectal cancer tissues". International Journal of Oncology 26.5 (2005): 1217-1226.
Chicago
Kim, B. N., Yamamoto, H., Ikeda, K., Damdinsuren, B., Sugita, Y., Ngan, C. Y., Fujie, Y., Ogawa, M., Hata, T., Ikeda, M., Ohue, M., Sekimoto, M., Monden, T., Matsuura, N., Monden, M."Methylation and expression of p16INK4 tumor suppressor gene in primary colorectal cancer tissues". International Journal of Oncology 26, no. 5 (2005): 1217-1226. https://doi.org/10.3892/ijo.26.5.1217