Sp1 expression regulates lung tumor progression

T. I. Hsu, M. C. Wang, S. Y. Chen, Y. M. Yeh, W. C. Su, W. C. Chang, J. J. Hung

Research output: Contribution to journalArticle

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Abstract

The role of specificity protein 1 (Sp1) in controlling gene expression in lung tumor development and metastasis is not well understood. In this study, we showed that the Sp1 level was highly increased and required for lung tumor growth in transgenic mice bearing Kras-induced lung tumors under the control of doxycycline. Furthermore, the Sp1 level was highly upregulated in lung adenocarcinoma cells with low invasiveness and in patients with stage I lung cancer. We also demonstrated that Sp1 was downregulated in lung adenocarcinoma cells with high invasiveness and in patients with stage IV lung adenocarcinoma. Moreover, Sp1 inversely regulated migration, invasion and metastasis of lung adenocarcinoma cells in vivo. In addition, a decrease in the Sp1 level in highly invasive lung adenocarcinoma cells resulted from instability of the Sp1 protein. Furthermore, overexpression of Sp1 in highly invasive lung adenocarcinoma cells increased expression of E-cadherin, a suppressor of metastasis, and attenuated the translocation of Β-catenin into the cellular nucleus that leads to tumor malignancy. Taken together, Sp1 level accumulated strongly in early stage and then declined in late stage, which is important for lung cancer cell proliferation and metastasis during tumorigenesis.

Original languageEnglish
Pages (from-to)3973-3988
Number of pages16
JournalOncogene
Volume31
Issue number35
DOIs
Publication statusPublished - Aug 30 2012

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Lung
Neoplasms
Proteins
Neoplasm Metastasis
Lung Neoplasms
Catenins
Doxycycline
Cadherins
Transgenic Mice
Adenocarcinoma of lung
Carcinogenesis
Down-Regulation
Cell Proliferation
Gene Expression
Growth

Keywords

  • E-cadherin
  • metastasis
  • Sp1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Hsu, T. I., Wang, M. C., Chen, S. Y., Yeh, Y. M., Su, W. C., Chang, W. C., & Hung, J. J. (2012). Sp1 expression regulates lung tumor progression. Oncogene, 31(35), 3973-3988. https://doi.org/10.1038/onc.2011.568

Sp1 expression regulates lung tumor progression. / Hsu, T. I.; Wang, M. C.; Chen, S. Y.; Yeh, Y. M.; Su, W. C.; Chang, W. C.; Hung, J. J.

In: Oncogene, Vol. 31, No. 35, 30.08.2012, p. 3973-3988.

Research output: Contribution to journalArticle

Hsu, TI, Wang, MC, Chen, SY, Yeh, YM, Su, WC, Chang, WC & Hung, JJ 2012, 'Sp1 expression regulates lung tumor progression', Oncogene, vol. 31, no. 35, pp. 3973-3988. https://doi.org/10.1038/onc.2011.568
Hsu TI, Wang MC, Chen SY, Yeh YM, Su WC, Chang WC et al. Sp1 expression regulates lung tumor progression. Oncogene. 2012 Aug 30;31(35):3973-3988. https://doi.org/10.1038/onc.2011.568
Hsu, T. I. ; Wang, M. C. ; Chen, S. Y. ; Yeh, Y. M. ; Su, W. C. ; Chang, W. C. ; Hung, J. J. / Sp1 expression regulates lung tumor progression. In: Oncogene. 2012 ; Vol. 31, No. 35. pp. 3973-3988.
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