Upregulation of ATF-3 is correlated with prognosis and proliferation of laryngeal cancer by regulating Cyclin D1 expression

Int J Clin Exp Pathol. 2013 Sep 15;6(10):2064-70. eCollection 2013.

Abstract

Objective: This study aimed to investigate the expression and significance of ATF-3 in laryngeal squamous cell carcinoma (LSCC).

Methods: Expression of ATF-3 was examined using immunohistochemistry methods in samples from 83 cases of LSCC carcinoma. MTT assay was used to detect proliferation of Hep-2 cells after ATF-3 knocked down by siRNA lentivirus. A mouse model was used to investigate the inhibitive role of ATF-3 siRNA in LSCC xenografts. Realtime RCR was used to detect Cyclin D1 expression after ATF-3 downregulation in Hep-2 cells.

Results: The expression of ATF-3 was positively detected in all the 83 cases of LSCC cancer tissues while Only 4 cases of adjacent non-neoplastic tissues were detected with positive ATF-3 expression. The ATF-3 expression was statistically related with T stage, neck nodal metastasis, clinical stage and prognosis of LSCC. Both cell proliferation in vitro and tumor growth in vivo were suppressed after ATF-3 knockdown. Furthermore, the expression of Cyclin D1 was decreased after ATF-3 downregulation in Hep-2 cells.

Conclusion: ATF-3 is involved in the progress of LSCC, and may provide clinical information for evaluation of prognosis of LSCC. The oncologic role of ATF-3 may be correlated with Cyclin D1 regulation.

Keywords: Cyclin D1; Laryngeal squamous cell carcinoma; activating transcription factor 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / genetics
  • Activating Transcription Factor 3 / metabolism*
  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Male
  • Mice
  • Prognosis
  • RNA, Small Interfering
  • Up-Regulation*

Substances

  • ATF3 protein, human
  • Activating Transcription Factor 3
  • RNA, Small Interfering
  • Cyclin D1