Thyroid transcription factor 1 represses the expression of Ki-67 and induces apoptosis in non-small cell lung cancer

Zu,Yun-Fen; Wang,Xi-Cai; Chen,Yan; Wang,Ji-Ying; Liu,Xin; Li,Xin; Li,Cheng-Wen; Xie,Yu-Cheng; Luo,Yan; Shang,Xie-Qin; Guo,Jing

doi:10.3892/or.2012.2009

November 2012 Volume 28 Issue 5

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November 2012 Volume 28 Issue 5

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Article Open Access

Thyroid transcription factor 1 represses the expression of Ki-67 and induces apoptosis in non-small cell lung cancer

Authors:
- Yun-Fen Zu
- Xi-Cai Wang
- Yan Chen
- Ji-Ying Wang
- Xin Liu
- Xin Li
- Cheng-Wen Li
- Yu-Cheng Xie
- Yan Luo
- Xie-Qin Shang
- Jing Guo
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Affiliations: Department of Oncology, Second People Hospital of Yunnan Province, Yunnan 650021, P.R. China, Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Yunnan 650118, P.R. China, Department of Research Management, The Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Yunnan 650118, P.R. China, Department of Pathology, Second People Hospital of Yunnan Province, Yunnan 650021, P.R. China

Copyright: © Zu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 1544-1550
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Published online on: August 31, 2012

https://doi.org/10.3892/or.2012.2009
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Abstract

The thyroid transcription factor 1 (TTF-1) gene is associated with the differentiation of lung epithelial cells and has been reported to be an independent prognostic factor for lung adenocarcinoma patients. The aim of the present study was to detect the expression of TTF-1 in human lung cancer cell lines and to evaluate the association of overexpressed TTF-1 with Ki-67 and apoptosis in the A549 cell line. We also investigated the expression of TTF-1 and Ki-67 in Xuanwei lung adenocarcinoma. TTF-1 mRNA expression was evaluated in 10 non-small cell lung cancer (NSCLC) cell lines by quantitative real-time RT-PCR (qRT-PCR). Overexpression of TTF-1 in A549 cells was achieved by transient transfection. The TTF-1 and Ki-67 proteins were detected by immunohistochemistry and apoptosis was detected by flow cytometry. We also investigated immunohistochemically the expression of TTF-1 and Ki-67 in 62 resected cases of Xuanwei lung adenocarcinoma. Overall the expression of TTF-1 mRNA in the 10 cell lines was low. Overexpression of TTF-1 mRNA was found only in 3 (30%) of 10 NSCLC cell lines, including 1 (25%) of 4 adenocarcinoma cell lines. A549 cells overexpressing TTF-1 were found to have repressed expression of Ki-67 (P=0.012) and increased apoptosis (P=0.000). Immunohistochemical analysis of resected cases of Xuanwei lung adenocarcinoma (n=62) showed the expression of TTF-1 in 58 (93%) of 62 and Ki-67 in 22 (35%) of 62. Patients with strong immunohistochemical expression TTF-1 were statistically associated with well-differentiated phenotype (P=0.006) and inverse correlation with Ki-67 expression (P=0.016). These data suggest that TTF-1 may serve as a tumor suppressor gene based on its inverse correlation with Ki-67 proliferative activity and increase of cellular apoptosis.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Thyroid transcription factor 1 represses the expression of Ki-67 and induces apoptosis in non-small cell lung cancer

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