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

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.