Abstract
The extremely dismal prognosis of pancreatic cancer (PC) is attributed, at least in part, to lack of early diagnosis. Therefore, identifying differentially expressed genes in multiple steps of tumorigenesis of PC is of great interest. In the present study, a 7,12-dimethylbenzanthraene (DMBA)-induced PC model was established in male Sprague-Dawley rats. The gene expression profile was screened using an oligonucleotide microarray, followed by real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemical staining validation. A total of 661 differentially expressed genes were identified in stages of pancreatic carcinogenesis. According to GO classification, these genes were involved in multiple molecular pathways. Using two-way hierarchical clustering analysis, normal pancreas, acute and chronic pancreatitis, PanIN, early and advanced pancreatic cancer were completely discriminated. Furthermore, 11 upregulated and 142 downregulated genes (probes) were found by Mann-Kendall trend Monotone test, indicating homologous genes of rat and human. The qRT-PCR and immunohistochemistry analysis of CXCR7 and UBe2c, two of the identified genes, confirmed the microarray results. In human PC cell lines, knockdown of CXCR7 resulted in decreased migration and invasion. Collectively, our data identified several promising markers and therapeutic targets of PC based on a comprehensive screening and systemic validation.
Highlights
Pancreatic cancer (PC) is a human solid malignant tumor with very poor prognosis [1]
Several clinical and pathological factors for PC have been identified, including T stage, lymph node/ distant metastasis, carbohydrate antigen (CA) 19-9 level and perineural/intraneural invasion; the factors affecting the prognosis of PC remain to be clarified [2,3,4,5]
We found that acinar cells can transdifferentiate to ductal cells in the tumorigenesis process in the DMBA-induced PC rat model [18]
Summary
Pancreatic cancer (PC) is a human solid malignant tumor with very poor prognosis [1]. One of the major drawbacks of the previous studies in human samples and cell lines is the difficulty to collect specimens in all stages of tumorigenesis. Chemical inducers of PC include N-nitrosobis(2-oxopropyl)amine, azaserine, and 7,12-dimethylbenzanthracene(DMBA) [6,7,8,9,10]. These models can induce the entire range of carcinogenesis, through advanced stage and metastasis. We found that acinar cells can transdifferentiate to ductal cells in the tumorigenesis process in the DMBA-induced PC rat model [18]. The screening of differentially expressed genes in this model has not been reported
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