Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation in human colon carcinoma cells

  • Authors:
    • Hikaru Izawa
    • Hirofumi Yamamoto
    • Bazarragchaa Damdinsuren
    • Kimimasa Ikeda
    • Masaki Tsujie
    • Rei Suzuki
    • Kotaro Kitani
    • Yosuke Seki
    • Taro Hayashi
    • Ichiro Takemasa
    • Masataka Ikeda
    • Masayuki Ohue
    • Mitsugu Sekimoto
    • Takushi Monden
    • Morito Monden
  • View Affiliations

  • Published online on: July 1, 2005     https://doi.org/10.3892/ijo.27.1.69
  • Pages: 69-76
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Abstract

The cyclin-dependent kinase inhibitor p21cip1/waf1 negatively regulates the progression of cell cycle and the potential usefulness of p21cip1/waf1 gene is proposed in gene therapy. However, studies have demonstrated a protective role of p21cip1/waf1 against apoptosis and little is known about effects of ectopic expression of p21cip1/waf1 on differentiation of colon cancer cells. In the present study, we found diffuse p21cip1/waf1 expression in only a few clinical samples of colorectal cancer with wild-type p53 gene. To explore the role of p21cip1/waf1 in cell growth, apoptosis and differentiation, we constitutively overexpressed p21cip1/waf1 in HT29 colon carcinoma cells. Ectopic overexpression of p21cip1/waf1 was associated with inhibition of CDK2-associated kinase activity, indicating the functionality of the introduced p21cip1/waf1 gene. Overexpression of p21cip1/waf1 caused an appreciable growth inhibition in monolayer and soft agar cultures and it significantly reduced sodium butyrate- but not 5-fluorouracil-induced apoptosis. p21cip1/waf1 overexpressing cells exhibited marked decrease of intestinal differentiation when assayed with intestinal alkaline phosphatase. Our findings suggest that introduction of p21cip1/waf1 gene into colon cancer cells may be useful for inhibiting cell growth but caution should be taken regarding the increased resistance to certain apoptosis-inducing agents and dysregulation of endogenous p21cip1/waf1-mediated differentiation process.

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July 2005
Volume 27 Issue 1

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

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Spandidos Publications style
Izawa H, Yamamoto H, Damdinsuren B, Ikeda K, Tsujie M, Suzuki R, Kitani K, Seki Y, Hayashi T, Takemasa I, Takemasa I, et al: Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation in human colon carcinoma cells. Int J Oncol 27: 69-76, 2005
APA
Izawa, H., Yamamoto, H., Damdinsuren, B., Ikeda, K., Tsujie, M., Suzuki, R. ... Monden, M. (2005). Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation in human colon carcinoma cells. International Journal of Oncology, 27, 69-76. https://doi.org/10.3892/ijo.27.1.69
MLA
Izawa, H., Yamamoto, H., Damdinsuren, B., Ikeda, K., Tsujie, M., Suzuki, R., Kitani, K., Seki, Y., Hayashi, T., Takemasa, I., Ikeda, M., Ohue, M., Sekimoto, M., Monden, T., Monden, M."Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation in human colon carcinoma cells". International Journal of Oncology 27.1 (2005): 69-76.
Chicago
Izawa, H., Yamamoto, H., Damdinsuren, B., Ikeda, K., Tsujie, M., Suzuki, R., Kitani, K., Seki, Y., Hayashi, T., Takemasa, I., Ikeda, M., Ohue, M., Sekimoto, M., Monden, T., Monden, M."Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation in human colon carcinoma cells". International Journal of Oncology 27, no. 1 (2005): 69-76. https://doi.org/10.3892/ijo.27.1.69