Tissue MicroArray analyses of pancreatic duodenal homeobox-1 in human cancers.
In previous studies, we demonstrated that rat insulin promoter (RIP)-driven gene therapy successfully targeted human pancreatic tumor PANC-1 cells and mouse insulinoma NIT-1 cells, which are both pancreatic duodenal homeobox-1 (PDX-1)-positive. The purpose of this study was to perform a human tissue array analysis to determine potential targets for RIP-driven gene therapy. A custom-designed tissue MicroArray analysis of various human cancer specimens was performed using a PDX-1 polyclonal antibody generated in our laboratory. The custom-designed Tissue MicroArray of human tumor specimens consists of human cancer specimens from different origins, such as the pancreas, breast, colon, prostate, kidney, liver, lung, and ovary. A panel of normal human specimens from 20 organs or tissues was used as a control. All tissues were fixed in formalin and embedded in paraffin. The immunohistochemistry studies of the cytoplasm and the nuclear expression levels were compared using the Loda method and blind reviews. Data are presented as the mean +/- SEM (p < 0.05 was considered significant by the unpaired student t-test). PDX-1 expression intensity was elevated in both benign and malignant tissues from the same patient with pancreas, breast, colon, prostate, and kidney cancers, whereas normal human tissues from control subjects without cancer did not express PDX-1. These results suggest that PDX-1 is an early marker for these cancers and could be potentially used as a diagnostic parameter and perhaps could be targeted by PDX-1-activated gene therapies, such as RIP-TK.
Wang
Xiao-Ping
XP
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin Street, Suite 1661, Houston, Texas 77030, USA.
Li
Zhi-Jun
ZJ
Magnusson
Jonas
J
Brunicardi
F Charles
FC
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D016022:Case-Control Studies; D005260:Female; D015316:Genetic Therapy; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D010195:Pancreatitis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein