Abstract
The c-jun oncogene is frequently overexpressed in non-small-cell lung cancers (NSCLC), but its functional involvement in lung cancer development has not been clearly elucidated. In this study, we found that among the immediate-early serum responsible genes, exemplified by c-jun, c-fos and c-myc, induction of c-jun in a human bronchial epithelial cell line, BEAS-2B, was dependent on anchorage, in contrast to clear induction of c-fos and c-myc under both anchorage-dependent and -independent conditions. In fact, forced expression of c-jun in BEAS-2B cells significantly increased cell viability and colony formation in soft agar. Furthermore, we also found that such anchorage-dependent regulation of c-jun was lost in a significant fraction of human lung cancer cell lines. Interestingly, suppressed anchorage-independent but not anchorage-dependent growth was noted by constitutive expression of a dominant-negative c-jun mutant in a lung cancer cell line showing dysregulated and sustained c-jun expression in the absence of anchorage. These findings suggest that dysregulated c-jun expression may be involved in the acquisition of anchorage independence in the process of human lung carcinogenesis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Amstad P, Reddel RR, Pfeifer A, Malan-Shibley L, Mark III GE, Harris CC . (1988). Mol Carcinog 1: 151–160.
Aoshiba K, Rennard SI, Spurzem JR . (1997). Am J Physiol 272: L28–L37.
Ben-Ezra JM, Kornstein MJ, Grimes MM, Krystal G . (1994). Am J Pathol 145: 1036–1040.
Brown PH, Alani R, Preis LH, Szabo E, Birrer MJ . (1993). Oncogene 8: 877–886.
Castellazzi M, Dangy JP, Mechta F, Hirai S, Yaniv M, Samarut J et al. (1990). Oncogene 5: 1541–1547.
Chen Y, Knosel T, Kristiansen G, Pietas A, Garber ME, Matsuhashi S et al. (2003). J Pathol 200: 640–646.
Cmarik JL, Min H, Hegamyer G, Zhan S, Kulesz-Martin M, Yoshinaga H et al. (1999). Proc Natl Acad Sci USA 96: 14037–14042.
Eferl R, Ricci R, Kenner L, Zenz R, David JP, Rath M et al. (2003). Cell 112: 181–192.
Feng H, Xiang H, Mao YW, Wang J, Liu JP, Huang XQ et al. (2004). Oncogene 23: 7310–7321.
Freedman VH, Shin SI . (1974). Cell 3: 355–359.
Frisch SM, Ruoslahti E . (1997). Curr Opin Cell Biol 9: 701–706.
Frisch SM, Screaton RA . (2001). Curr Opin Cell Biol 13: 555–562.
Fujita M, Shiku H . (1995). Oncogene 11: 15–20.
Hida T, Ueda R, Takahashi T, Watanabe H, Kato T, Suyama M et al. (1989). Cancer Res 49: 4785–4790.
Hommura F, Katabami M, Leaner VD, Donninger H, Sumter TF, Resar LM et al. (2004). Mol Cancer Res 2: 305–314.
Ikegaki N, Katsumata M, Minna J, Tsujimoto Y . (1994). Cancer Res 54: 6–8.
Katabami M, Donninger H, Hommura F, Leaner VD, Kinoshita I, Chick JF et al. (2005). J Biol Chem 280: 16728–16738.
Kinoshita I, Leaner V, Katabami M, Manzano RG, Dent P, Sabichi A et al. (2003). Oncogene 22: 2710–2722.
Lu A, Zhang F, Gupta A, Liu J . (2002). J Biol Chem 277: 31364–31372.
Masuda A, Kondo M, Saito T, Yatabe Y, Kobayashi T, Okamoto M et al. (1997). Cancer Res 57: 4898–4904.
Muller R, Bravo R, Burckhardt J, Curran T . (1984). Nature 312: 716–720.
Ookawa K, Tsuchida S, Adachi J, Yokota J . (1997). Oncogene 14: 1389–1396.
Osada H, Takahashi T . (2002). Oncogene 21: 7421–7434.
Reddel RR, De Silva R, Duncan EL, Rogan EM, Whitaker NJ, Zahra DG et al. (1995). Int J Cancer 61: 199–205.
Reddel RR, Ke Y, Gerwin BI, McMenamin MG, Lechner JF, Su RT et al. (1988a). Cancer Res 48: 1904–1909.
Reddel RR, Ke Y, Kaighn ME, Malan-Shibley L, Lechner JF, Rhim JS et al. (1988b). Oncogene Res 3: 401–408.
Rodenhuis S, van de Wetering ML, Mooi WJ, Evers SG, van Zandwijk N, Bos JL . (1987). N Engl J Med 317: 929–935.
Schutte J, Minna JD, Birrer MJ . (1989). Proc Natl Acad Sci USA 86: 2257–2261.
Shaulian E, Karin M . (2002). Nat Cell Biol 4: E131–E136.
Suzuki T, Hashimoto Y, Okuno H, Sato H, Nishina H, Iba H . (1991). Jpn J Cancer Res 82: 58–64.
Szabo E, Riffe ME, Steinberg SM, Birrer MJ, Linnoila RI . (1996). Cancer Res 56: 305–315.
Vogt PK . (2001). Oncogene 20: 2365–2377.
Wodrich W, Volm M . (1993). Carcinogenesis 14: 1121–1124.
Yanagisawa K, Osada H, Masuda A, Kondo M, Saito T, Yatabe Y et al. (1998). Oncogene 17: 1743–1747.
Yang HS, Knies JL, Stark C, Colburn NH . (2003). Oncogene 22: 3712–3720.
Young MR, Li JJ, Rincon M, Flavell RA, Sathyanarayana BK, Hunziker R et al. (1999). Proc Natl Acad Sci USA 96: 9827–9832.
Acknowledgements
We thank Dr John D Minna for pVcos-7neo-c-jun, Dr Curtis C Harris (National Cancer Center Institute) for BEAS-2B cells, Dr Jun Yokota (National Cancer Center Research Institute) for pTA-hyg and pT2GN, Dr Masatoshi Fujita for pLfosSN (National Cancer Center Research Institute) and Dr Motoshi Suzuki for critical reading of this manuscript. Grant support: This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Maeno, K., Masuda, A., Yanagisawa, K. et al. Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers. Oncogene 25, 271–277 (2006). https://doi.org/10.1038/sj.onc.1209018
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209018
Keywords
This article is cited by
-
APE1 modulates cellular responses to organophosphate pesticide-induced oxidative damage in non-small cell lung carcinoma A549 cells
Molecular and Cellular Biochemistry (2018)
-
Emerging roles of ATF2 and the dynamic AP1 network in cancer
Nature Reviews Cancer (2010)
-
Simultaneous blockade of AP-1 and phosphatidylinositol 3-kinase pathway in non-small cell lung cancer cells
British Journal of Cancer (2008)
-
Growth inhibition of non-small cell lung cancer cells by AP-1 blockade using a cJun dominant-negative mutant
British Journal of Cancer (2008)
-
Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice
Gene Therapy (2007)