Protective function of p27 KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments

Akira Masuda, Hirotaka Osada, Yasushi Yatabe, Ken Ichi Kozaki, Yoshio Tatematsu, Takao Takahashi, Toyoaki Hida, Toshitada Takahashi, Takashi Takahashi

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33 Citations (Scopus)

Abstract

A previous study of ours unexpectedly found that in contrast to frequent reductions in non-small cell lung cancer, high expression of the p27 KIP1 cyclin-dependent kinase (CDK) inhibitor was retained in virtually all small cell lung cancers (SCLCs), suggesting the possibility of high expression of nonfunctional p27 KIP1 in this virulent tumor. The study presented here, however, shows that p27 KIP1 in SCLC biochemically functions as a CDK inhibitor, clearly showing induction apparently associated with G 1 /G 0 arrest and efficient binding to and inhibition of the cyclin E-CDK2 complex. Interestingly, induction of p27 KIP1 seems to confer on SCLC cells the ability to survive under culture conditions unfavorable for cell growth such as a lack of nutrients and hypoxia. Subsequent experiments manipulating p27 KIP1 levels by using a sense p27 KIP1 expression construct or an antisense oligonucleotide supported this notion. These observations suggest that high expression of p27 KIP1 in vivo may favor the survival of SCLC by preventing apoptosis in a microenvironment unfavorable for cell proliferation.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalAmerican Journal of Pathology
Volume158
Issue number1
DOIs
Publication statusPublished - Jan 2001

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Masuda, A., Osada, H., Yatabe, Y., Kozaki, K. I., Tatematsu, Y., Takahashi, T., Hida, T., Takahashi, T., & Takahashi, T. (2001). Protective function of p27 KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments American Journal of Pathology, 158(1), 87-96. https://doi.org/10.1016/S0002-9440(10)63947-8