Human Pituitary Tumor Transforming Gene (hPTTG) Inhibits Human Lung Cancer A549 Cell Growth through Activation of p21 WAF1/CIP1

Yi Ming Mu, Koichi Oba, Toshihiko Yanase, Takeshi Ito, Kenji Ashida, Kiminobu Goto, Hidetaka Morinaga, Shoichiro Ikuyama, Ryoichi Takayanagi, Hajime Nawata

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [ 3 H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21 WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21 WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21 WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21 WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21 WAF1/CIP1 -dependent and -independent.

Original languageEnglish
Pages (from-to)771-781
Number of pages11
JournalEndocrine Journal
Volume50
Issue number6
DOIs
Publication statusPublished - Dec 1 2003

Fingerprint

Pituitary Neoplasms
Oncogenes
Lung Neoplasms
Growth
HeLa Cells
A549 Cells
Messenger RNA
Proto-Oncogenes
Luciferases
Northern Blotting
Thymidine
Agar
Transfection
Cytoplasm
Western Blotting
Apoptosis

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Human Pituitary Tumor Transforming Gene (hPTTG) Inhibits Human Lung Cancer A549 Cell Growth through Activation of p21 WAF1/CIP1 . / Mu, Yi Ming; Oba, Koichi; Yanase, Toshihiko; Ito, Takeshi; Ashida, Kenji; Goto, Kiminobu; Morinaga, Hidetaka; Ikuyama, Shoichiro; Takayanagi, Ryoichi; Nawata, Hajime.

In: Endocrine Journal, Vol. 50, No. 6, 01.12.2003, p. 771-781.

Research output: Contribution to journalArticle

Mu, YM, Oba, K, Yanase, T, Ito, T, Ashida, K, Goto, K, Morinaga, H, Ikuyama, S, Takayanagi, R & Nawata, H 2003, ' Human Pituitary Tumor Transforming Gene (hPTTG) Inhibits Human Lung Cancer A549 Cell Growth through Activation of p21 WAF1/CIP1 ', Endocrine Journal, vol. 50, no. 6, pp. 771-781. https://doi.org/10.1507/endocrj.50.771
Mu, Yi Ming ; Oba, Koichi ; Yanase, Toshihiko ; Ito, Takeshi ; Ashida, Kenji ; Goto, Kiminobu ; Morinaga, Hidetaka ; Ikuyama, Shoichiro ; Takayanagi, Ryoichi ; Nawata, Hajime. / Human Pituitary Tumor Transforming Gene (hPTTG) Inhibits Human Lung Cancer A549 Cell Growth through Activation of p21 WAF1/CIP1 In: Endocrine Journal. 2003 ; Vol. 50, No. 6. pp. 771-781.
@article{77e156b3a5fb406b8af0259f473484ff,
title = "Human Pituitary Tumor Transforming Gene (hPTTG) Inhibits Human Lung Cancer A549 Cell Growth through Activation of p21 WAF1/CIP1",
abstract = "Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [ 3 H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21 WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21 WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21 WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21 WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21 WAF1/CIP1 -dependent and -independent.",
author = "Mu, {Yi Ming} and Koichi Oba and Toshihiko Yanase and Takeshi Ito and Kenji Ashida and Kiminobu Goto and Hidetaka Morinaga and Shoichiro Ikuyama and Ryoichi Takayanagi and Hajime Nawata",
year = "2003",
month = "12",
day = "1",
doi = "10.1507/endocrj.50.771",
language = "English",
volume = "50",
pages = "771--781",
journal = "Endocrine Journal",
issn = "0918-8959",
publisher = "Japan Endocrine Society",
number = "6",

}

TY - JOUR

T1 - Human Pituitary Tumor Transforming Gene (hPTTG) Inhibits Human Lung Cancer A549 Cell Growth through Activation of p21 WAF1/CIP1

AU - Mu, Yi Ming

AU - Oba, Koichi

AU - Yanase, Toshihiko

AU - Ito, Takeshi

AU - Ashida, Kenji

AU - Goto, Kiminobu

AU - Morinaga, Hidetaka

AU - Ikuyama, Shoichiro

AU - Takayanagi, Ryoichi

AU - Nawata, Hajime

PY - 2003/12/1

Y1 - 2003/12/1

N2 - Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [ 3 H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21 WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21 WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21 WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21 WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21 WAF1/CIP1 -dependent and -independent.

AB - Pituitary tumor transforming gene (PTTG) is a proto-oncogene cloned from rat GH4 cells. This gene was able to induce cell transformation in vitro and is also associated with p53-dependent and -independent apoptosis. In this study, we cloned human PTTG (hPTTG) from a pituitary tumor and then stably transfected the hPTTG into HeLa and A549 cells. An overexpression of hPTTG significantly inhibited cell growth, which was determined by the adherent cell growth properties, colony formation in soft agar and [ 3 H] thymidine incorporation, respectively, in HeLa and A549 cells. The inhibitory effect on cell growth was associated with the activation of p21 WAF1/CIP1 in A549 cells, but not in HeLa cells. The hPTTG overexpression increased both the p21 WAF1/CIP1 mRNA and protein expression levels as determined by both Northern and Western blot analysis, respectively, in A549 cells. The increased expression of p21 WAF1/CIP1 mRNA was regulated at the transcription level and was independent on p53 expression because the luciferase activity increased after the co-transfection of hPTTG and p21 WAF1/CIP1 promoter fragments with and without a p53 binding sequence. The subcellular distribution of hPTTG was dependent on cell type, and was predominantly in the nucleus in HeLa, Cos-7 and DU145 cells, but showed a diffuse distribution in both the nucleus and cytoplasm in A549, DLD-1 and NIH3T3 cells. These results indicate that an overexpression of hPTTG inhibits the cell growth due to different mechanisms, which are p21 WAF1/CIP1 -dependent and -independent.

UR - http://www.scopus.com/inward/record.url?scp=9144262954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9144262954&partnerID=8YFLogxK

U2 - 10.1507/endocrj.50.771

DO - 10.1507/endocrj.50.771

M3 - Article

VL - 50

SP - 771

EP - 781

JO - Endocrine Journal

JF - Endocrine Journal

SN - 0918-8959

IS - 6

ER -