Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer patients: A mechanism of proliferation and apoptosis in cancer

Ma,Jie; Li,Jia; Li,Hua; Xiao,Xigang; Shen,Lei; Fang,Lin

doi:10.3892/mmr.2012.1067

November 2012 Volume 6 Issue 5

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November 2012 Volume 6 Issue 5

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Article

Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer patients: A mechanism of proliferation and apoptosis in cancer

Authors:
- Jie Ma
- Jia Li
- Hua Li
- Xigang Xiao
- Lei Shen
- Lin Fang
View Affiliations / Copyright

Affiliations: Department of Breast and Thyroid Surgery, Tenth People's Hospital of Tongji University, Zhabei, Shanghai 200072, P.R. China
Pages: 983-988
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Published online on: September 5, 2012

https://doi.org/10.3892/mmr.2012.1067
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Abstract

Pancreatic-duodenal homeobox 1 (PDX-1) is a transcription factor that regulates embryological pancreas development and insulin expression in adult islets. The current study investigated the expression profile and potential role of PDX-1 in breast cancer. Immunohistochemistry was performed to determine the expression pattern of PDX-1 in breast cancer and adjacent benign breast tissues. In addition, cell proliferation and the cell cycle were evaluated following the transient inhibition of PDX-1 with antisense oligonucleotides in MCF-7 human breast cancer cells. Real-time PCR and western blotting were conducted to investigate the correlation between PDX-1, P53, Ki-67, Caspase 3 and Caspase 8. These experiments demonstrated that PDX-1 was downregulated in human breast cancer tissue compared with adjacent normal breast tissue. Knockdown of PDX-1 expression in vitro in MCF-7 breast cancer cells promoted cell proliferation and disrupted the cell cycle, as demonstrated by the overexpression of P53 and Ki-67 at the mRNA and protein levels. In conclusion, the current study shows that PDX-1 regulates cell proliferation and the cell cycle in human breast cancer cells by altering the expression of the cell cycle-related genes, P53 and Ki-67. These data suggest that PDX-1 is a putative tumor suppressor in breast cancer.

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1	Schwitzgebel VM, Mamin A, Brun T, et al: Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. J Clin Endocrinol Metab. 88:4398–4406. 2003. View Article : Google Scholar : PubMed/NCBI
2	Fukuda A, Kawaguchi Y, Furuyama K, et al: Loss of the major duodenal papilla results in brown pigment biliary stone formation in pdx1 null mice. Gastroenterology. 130:855–867. 2006. View Article : Google Scholar : PubMed/NCBI
3	Gannon M, Tweedie Ables E, Crawford L, et al: Pdx-1 function is specifically required in embryonic β cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol. 314:406–417. 2008.
4	Ashizawa S, Brunicardi FC and Wang XP: PDX-1 and the pancreas. Pancreas. 28:109–120. 2004. View Article : Google Scholar
5	Offield MF, Jetton TL, Labosky PA, et al: PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development. 122:983–995. 1996.PubMed/NCBI
6	Liu T, Gou SM, Wang CY, et al: Pancreas duodenal homeobox-1 expression and significance in pancreatic cancer. World J Gastroenterol. 13:2615–2618. 2007. View Article : Google Scholar : PubMed/NCBI
7	Jonmarker S, Glaessgen A, Culp WD, et al: Expression of PDX-1 in prostate cancer, prostatic intraepithelial neoplasia and benign prostatic tissue. APMIS. 116:491–498. 2008. View Article : Google Scholar : PubMed/NCBI
8	Leys CM, Nomura S, Rudzinski E, et al: Expression of PDX-1 in human gastric metaplasia and gastric adenocacinoma. Hum Pathol. 37:1162–1168. 2006. View Article : Google Scholar : PubMed/NCBI
9	Sakai H, Eishi Y, Li XL, et al: PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas. Gut. 53:323–330. 2004. View Article : Google Scholar : PubMed/NCBI
10	Ballian N, Liu SH and Brunicardi FC: Transcription factor PDX-1 in human colorectal adenocarcinoma: A potential tumor maker. World J Gastroenterol. 14:5823–5826. 2008. View Article : Google Scholar : PubMed/NCBI
11	Wang XP, Li ZJ, Magnusson J, et al: Tissue microarray of pancreatic duodenal homeo-box-1 in human cancers. World J Surg. 29:334–338. 2005. View Article : Google Scholar
12	Tirone TA, Wang XP, Templeton NS, et al: Cell-specific cytotoxicity of human pancreatic adenocarcinoma cells using rat insulin promoter thymidine kinase directed gene therapy. WJ Surg. 28:826–833. 2004. View Article : Google Scholar
13	Liu SH, Patel S, Gingras MC, et al: PDX-1: demonstration of oncogenic properties in pancreatic cancer. Cancer. 117:723–733. 2011. View Article : Google Scholar : PubMed/NCBI
14	Koizumi M, Doi R, Toyoda E, et al: Increased PDX-1 expression is associated with outcome in patients with pancreatic cancer. Surgery. 134:260–266. 2003. View Article : Google Scholar : PubMed/NCBI
15	Quint K, Stintzing S, Alinger B, et al: The expression pattern of PDX-1, SHH, Patched and Gli-1 is associated with pathological and clinical features in human pancreatic cancer. Pancreatology. 9:116–126. 2009. View Article : Google Scholar : PubMed/NCBI
16	Ma J, Chen M, Wang J, et al: Pancreatic duodenal homeobox-1 (PDX1) functions as a tumor suppressor in gastric cancer. Carcinogenesis. 29:1327–1333. 2008. View Article : Google Scholar : PubMed/NCBI
17	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods. 25:402–408. 2001.
18	World Health Organization. Cancer fact sheet No. 297. Geneva: 2006

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

Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer patients: A mechanism of proliferation and apoptosis in cancer

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