Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments

A. Masuda, H. Osada, Y. Yatabe, K. I. Kozaki, Y. Tatematsu, T. Takahashi, T. Hida, T. Takahashi, T. Takahashi

Research output: Contribution to journalArticle

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 p27KIP1 cyclin-dependent kinase (CDK) inhibitor was retained in virtually all small cell lung cancers (SCLCs), suggesting the possibility of high expression of nonfunctional p27KIP1 in this virulent tumor. The study presented here, however, shows that p27KIP1 in SCLC biochemically functions as a CDK inhibitor, clearly showing induction apparently associated with G1/G0 arrest and efficient binding to and inhibition of the cyclin E-CDK2 complex. Interestingly, induction of p27KIP1 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 p27KIP1 levels by using a sense p27KIP1 expression construct or an antisense oligonucleotide supported this notion. These observations suggest that high expression of p27KIP1 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
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Small Cell Lung Carcinoma
Apoptosis
Cyclin-Dependent Kinases
Cyclin E
Antisense Oligonucleotides
Non-Small Cell Lung Carcinoma
Cell Proliferation
Food
Growth
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Masuda, A., Osada, H., Yatabe, Y., Kozaki, K. I., Tatematsu, Y., Takahashi, T., ... Takahashi, T. (2001). Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments. American Journal of Pathology, 158(1), 87-96.

Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments. / Masuda, A.; Osada, H.; Yatabe, Y.; Kozaki, K. I.; Tatematsu, Y.; Takahashi, T.; Hida, T.; Takahashi, T.; Takahashi, T.

In: American Journal of Pathology, Vol. 158, No. 1, 2001, p. 87-96.

Research output: Contribution to journalArticle

Masuda, A, Osada, H, Yatabe, Y, Kozaki, KI, Tatematsu, Y, Takahashi, T, Hida, T, Takahashi, T & Takahashi, T 2001, 'Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments', American Journal of Pathology, vol. 158, no. 1, pp. 87-96.
Masuda, A. ; Osada, H. ; Yatabe, Y. ; Kozaki, K. I. ; Tatematsu, Y. ; Takahashi, T. ; Hida, T. ; Takahashi, T. ; Takahashi, T. / Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments. In: American Journal of Pathology. 2001 ; Vol. 158, No. 1. pp. 87-96.
@article{99b5eee46ea84bdc92cb0c90ce33f4f1,
title = "Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments",
abstract = "A previous study of ours unexpectedly found that in contrast to frequent reductions in non-small cell lung cancer, high expression of the p27KIP1 cyclin-dependent kinase (CDK) inhibitor was retained in virtually all small cell lung cancers (SCLCs), suggesting the possibility of high expression of nonfunctional p27KIP1 in this virulent tumor. The study presented here, however, shows that p27KIP1 in SCLC biochemically functions as a CDK inhibitor, clearly showing induction apparently associated with G1/G0 arrest and efficient binding to and inhibition of the cyclin E-CDK2 complex. Interestingly, induction of p27KIP1 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 p27KIP1 levels by using a sense p27KIP1 expression construct or an antisense oligonucleotide supported this notion. These observations suggest that high expression of p27KIP1 in vivo may favor the survival of SCLC by preventing apoptosis in a microenvironment unfavorable for cell proliferation.",
author = "A. Masuda and H. Osada and Y. Yatabe and Kozaki, {K. I.} and Y. Tatematsu and T. Takahashi and T. Hida and T. Takahashi and T. Takahashi",
year = "2001",
language = "English",
volume = "158",
pages = "87--96",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Protective function of p27KIP1 against apoptosis in small cell lung cancer cells in unfavorable microenvironments

AU - Masuda, A.

AU - Osada, H.

AU - Yatabe, Y.

AU - Kozaki, K. I.

AU - Tatematsu, Y.

AU - Takahashi, T.

AU - Hida, T.

AU - Takahashi, T.

AU - Takahashi, T.

PY - 2001

Y1 - 2001

N2 - A previous study of ours unexpectedly found that in contrast to frequent reductions in non-small cell lung cancer, high expression of the p27KIP1 cyclin-dependent kinase (CDK) inhibitor was retained in virtually all small cell lung cancers (SCLCs), suggesting the possibility of high expression of nonfunctional p27KIP1 in this virulent tumor. The study presented here, however, shows that p27KIP1 in SCLC biochemically functions as a CDK inhibitor, clearly showing induction apparently associated with G1/G0 arrest and efficient binding to and inhibition of the cyclin E-CDK2 complex. Interestingly, induction of p27KIP1 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 p27KIP1 levels by using a sense p27KIP1 expression construct or an antisense oligonucleotide supported this notion. These observations suggest that high expression of p27KIP1 in vivo may favor the survival of SCLC by preventing apoptosis in a microenvironment unfavorable for cell proliferation.

AB - A previous study of ours unexpectedly found that in contrast to frequent reductions in non-small cell lung cancer, high expression of the p27KIP1 cyclin-dependent kinase (CDK) inhibitor was retained in virtually all small cell lung cancers (SCLCs), suggesting the possibility of high expression of nonfunctional p27KIP1 in this virulent tumor. The study presented here, however, shows that p27KIP1 in SCLC biochemically functions as a CDK inhibitor, clearly showing induction apparently associated with G1/G0 arrest and efficient binding to and inhibition of the cyclin E-CDK2 complex. Interestingly, induction of p27KIP1 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 p27KIP1 levels by using a sense p27KIP1 expression construct or an antisense oligonucleotide supported this notion. These observations suggest that high expression of p27KIP1 in vivo may favor the survival of SCLC by preventing apoptosis in a microenvironment unfavorable for cell proliferation.

UR - http://www.scopus.com/inward/record.url?scp=0035144958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035144958&partnerID=8YFLogxK

M3 - Article

C2 - 11141482

AN - SCOPUS:0035144958

VL - 158

SP - 87

EP - 96

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -