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Growth inhibition of non-small cell lung cancer cells by AP-1 blockade using a cJun dominant-negative mutant.

Shimizu Y, Kinoshita I, Kikuchi J, Yamazaki K, Nishimura M, Birrer MJ, Dosaka-Akita H - Br. J. Cancer (2008)

Bottom Line: The colony-forming efficiency of H1299 and A549 was reduced by TAM67, while that of H520 was not.The induced TAM67 decreased the expression of a cell-cycle regulatory protein, cyclin A.Furthermore, TAM67 reduced growth of established xenograft tumours from these cells in nude mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.

ABSTRACT
cJun, a major constituent of AP-1 transcription factor transducing multiple mitogen growth signals, is frequently overexpressed in non-small cell lung cancers (NSCLCs). The purpose of this study is to determine the effects of AP-1 blockade on the growth of NSCLC cells using a cJun dominant-negative mutant, TAM67. Transiently transfected TAM67 inhibited AP-1 transcriptional activity in NSCLC cell lines, NCI-H1299 (H1299), A549 and NCI-H520 (H520). The colony-forming efficiency of H1299 and A549 was reduced by TAM67, while that of H520 was not. To elucidate the effects of TAM67 on the growth of H1299, we established H1299 clone cells that expressed TAM67 under the control of a doxycycline-inducible promoter. In the H1299 clone cells, the induced TAM67 inhibited anchorage-dependent growth by promoting G1 cell-cycle block, but not by apoptosis. The induced TAM67 decreased the expression of a cell-cycle regulatory protein, cyclin A. TAM67 also inhibited anchorage-independent growth of these cells. Furthermore, TAM67 reduced growth of established xenograft tumours from these cells in nude mice. These results suggest that AP-1 plays an essential role in the growth of at least some of NSCLC cells.

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Inhibition of anchorage-independent growth under the induction of TAM67. H1299 Tet-on clone cells were cultured in soft agarose in the absence or presence of doxycycline for 2 weeks. Each value represents the mean±s.d. (n=3). *P<0.01.
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fig7: Inhibition of anchorage-independent growth under the induction of TAM67. H1299 Tet-on clone cells were cultured in soft agarose in the absence or presence of doxycycline for 2 weeks. Each value represents the mean±s.d. (n=3). *P<0.01.

Mentions: We determined whether TAM67 inhibits anchorage-independent growth by soft agar assay. As shown in Figure 7, the growth of TAM67 #8 and TAM67 #34 was suppressed remarkably in the presence of doxycycline, but not in GFP #1 and GFP #3. These results indicate that anchorage-independent growth, as well as anchorage-dependent growth, is inhibited by TAM67.


Growth inhibition of non-small cell lung cancer cells by AP-1 blockade using a cJun dominant-negative mutant.

Shimizu Y, Kinoshita I, Kikuchi J, Yamazaki K, Nishimura M, Birrer MJ, Dosaka-Akita H - Br. J. Cancer (2008)

Inhibition of anchorage-independent growth under the induction of TAM67. H1299 Tet-on clone cells were cultured in soft agarose in the absence or presence of doxycycline for 2 weeks. Each value represents the mean±s.d. (n=3). *P<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2266861&req=5

fig7: Inhibition of anchorage-independent growth under the induction of TAM67. H1299 Tet-on clone cells were cultured in soft agarose in the absence or presence of doxycycline for 2 weeks. Each value represents the mean±s.d. (n=3). *P<0.01.
Mentions: We determined whether TAM67 inhibits anchorage-independent growth by soft agar assay. As shown in Figure 7, the growth of TAM67 #8 and TAM67 #34 was suppressed remarkably in the presence of doxycycline, but not in GFP #1 and GFP #3. These results indicate that anchorage-independent growth, as well as anchorage-dependent growth, is inhibited by TAM67.

Bottom Line: The colony-forming efficiency of H1299 and A549 was reduced by TAM67, while that of H520 was not.The induced TAM67 decreased the expression of a cell-cycle regulatory protein, cyclin A.Furthermore, TAM67 reduced growth of established xenograft tumours from these cells in nude mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.

ABSTRACT
cJun, a major constituent of AP-1 transcription factor transducing multiple mitogen growth signals, is frequently overexpressed in non-small cell lung cancers (NSCLCs). The purpose of this study is to determine the effects of AP-1 blockade on the growth of NSCLC cells using a cJun dominant-negative mutant, TAM67. Transiently transfected TAM67 inhibited AP-1 transcriptional activity in NSCLC cell lines, NCI-H1299 (H1299), A549 and NCI-H520 (H520). The colony-forming efficiency of H1299 and A549 was reduced by TAM67, while that of H520 was not. To elucidate the effects of TAM67 on the growth of H1299, we established H1299 clone cells that expressed TAM67 under the control of a doxycycline-inducible promoter. In the H1299 clone cells, the induced TAM67 inhibited anchorage-dependent growth by promoting G1 cell-cycle block, but not by apoptosis. The induced TAM67 decreased the expression of a cell-cycle regulatory protein, cyclin A. TAM67 also inhibited anchorage-independent growth of these cells. Furthermore, TAM67 reduced growth of established xenograft tumours from these cells in nude mice. These results suggest that AP-1 plays an essential role in the growth of at least some of NSCLC cells.

Show MeSH
Related in: MedlinePlus