Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers

Maeno, Ken; Masuda, Akira; Yanagisawa, Kiyoshi; Konishi, Hiroyuki; Osada, Hiroyuki; Saito, Toshiko; Ueda, Ryuzo; Takahashi, Takashi

doi:10.1038/sj.onc.1209018

Cited by 33 publications

(26 citation statements)

References 32 publications

(42 reference statements)

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“…Suppression of the anchorage-independent growth of H1299 NSCLC cells by AP-1 blockade is consistent with previous reports using another NSCLC cell line (Maeno et al, 2006). Furthermore, we demonstrate that in vivo tumour growth of the NSCLC cells is also suppressed by AP-1 blockade.…”

Section: Discussionsupporting

confidence: 81%

“…Recently, it has been reported that forced expression of cJun increases anchorage-independent growth in a human bronchial epithelial cell line and that constitutive expression of a dominantnegative mutant of cJun inhibits anchorage-independent but not anchorage-dependent growth of a lung cancer cell line (Maeno et al, 2006). These findings suggest rather restrictive roles of cJun in the acquisition of anchorage independence in the process of human lung carcinogenesis.…”

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confidence: 62%

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

et al. 2008

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cJun, a major constituent of AP-1 transcription factor transducing multiple mitogen growth signals, is frequently overexpressed in nonsmall 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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Section: Discussionsupporting

confidence: 81%

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confidence: 62%

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

et al. 2008

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“…Maeno et al (2006) reported that deregulated c-Jun expression was involved in the acquisition of anchorage independence in human lung carcinogenesis . Activated PI3K signalling plays a critical role in protecting cells from anoikis by inactivating certain key apoptotic molecules and simultaneously enhancing anchorage-independent cell cycle progression by inhibiting the cyclin inhibitors and enhancing certain CDK activity (Wang, 2004).…”

Section: Discussionmentioning

confidence: 99%

Simultaneous blockade of AP-1 and phosphatidylinositol 3-kinase pathway in non-small cell lung cancer cells

et al. 2008

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c-Jun is a major constituent of AP-1 transcription factor that transduces multiple mitogen growth signals, and it is frequently overexpressed in non-small cell lung cancers (NSCLCs). Earlier, we showed that blocking AP-1 by the overexpression of a c-Jun dominant-negative mutant, TAM67, inhibited NSCLC cell growth. The phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathway is important in transformation, proliferation, survival and metastasis of NSCLC cells. In this study, we used NCI-H1299 Tet-on clone cells that express TAM67 under the control of inducible promoter to determine the effects of inhibition of AP-1 and PI3K on cell growth. The PI3K inhibitor, LY294002, produced a dose-dependent inhibition of growth in H1299 cells and that inhibition was enhanced by TAM67. TAM67 increased dephosphorylation of Akt induced by LY294002 and reduced the TPA response element DNA-binding of phosphorylated c-Jun. TAM67 increased G1 cell cycle blockade induced by LY294002, which was partially associated with cyclin A decrease and p27 Kip1 accumulation. Furthermore, TAM67 and LY294002 act, at least additively, to inhibit anchorage-independent growth of the H1299 cells. These results suggest that AP-1 and PI3K/Akt pathways play an essential role in the growth of some NSCLC cells.

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“…(c) Northern blot analysis showing significant inhibition of miR-18a, miR-19a and miR-92-1 by their corresponding antisense ON treatments. A human lung cancer cell line, Calu6 overexpressing miR-17-92 (Hayashita et al, 2005), was cultured with RPMI 1640/5% FCS at 371C with 5% CO 2 as previously described (Maeno et al, 2006). Cells were plated at 1 Â 10 6 in 10 cm dishes on day 1, and each ON was transfected at 10 nM with Lipofectamine 2000 (Invitrogen) on day 2.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92

et al. 2007

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Amplification and overexpression of the miR-17-92 microRNAs (miRNA) cluster at 13q31.3 has recently reported, with pointers to functional involvement in the development of B-cell lymphomas and lung cancers. In the present study, we show that inhibition of miR-17-5p and miR-20a with antisense oligonucleotides (ONs) can induce apoptosis selectively in lung cancer cells overexpressing miR-17-92, suggesting the possibility of 'OncomiR addiction' to expression of these miRNAs in a subset of lung cancers. In marked contrast, antisense ONs against miR18a and miR-19a did not exhibit such inhibitory effects, whereas inhibition of miR-92-1 resulted in only modest reduction of cell growth, showing significant distinctions among miRNAs of the miR-17-92 cluster in terms of their roles in cancer cell growth. During the course of this study, we also found that enforced expression of a genomic region, termed C2, residing 3 0 to miR-17-92 in the intron 3 of C13orf25 led to marked growth inhibition in association with double stranded RNA-dependent protein kinase activation. Finally, this study also revealed that the vast majority of C13orf25 transcripts are detected as Drosha-processed cleavage products on Northern blot analysis and that a novel polyadenylation site is present 3 0 to the miR-17-92 cluster and 5 0 to the C2 region. Taken together, the present findings contribute towards better understanding of the oncogenic roles of miR-17-92, which might ultimately lead to the future translation into clinical applications.

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Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers

Cited by 33 publications

References 32 publications

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

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

Simultaneous blockade of AP-1 and phosphatidylinositol 3-kinase pathway in non-small cell lung cancer cells

Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92

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