Non-collagenous extracellular matrix protein dermatopontin may play a role as another component of transforming growth factor-β signaling pathway in colon carcinogenesis

Document Type : Original Article

Authors

1 Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Human Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Iranian Academic Centers for Education, Culture, and Research (ACECR)

4 Department of Pathology, Faculty of Medicine, Mashhad, University of Medical Sciences, Mashhad, Iran

5 Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

6 Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

7 Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, München, Germany

Abstract

Objective(s): Dermatopontin (DPT) is an extracellular matrix protein that plays roles in increasing the activity of transforming growth factor-β (TGF-β) and induction of cell quiescence. These roles suggest a tumor suppressor function for DPT. This study aimed to investigate changes in DPT gene expression in colorectal cancer providing a better understanding of its carcinogenesis.
Materials and Methods: We used Matched Tumor/Normal Expression Array and Cancer Profiling Arrays I containing 34 and 7 cases of colorectal cancer and their matched controls, respectively, to test DPT expression. In addition, 38 newly diagnosed cases of colorectal cancer were enrolled and their fresh colonic tumoral and normal specimens were obtained. DPT mRNA expression was analyzed using real-time PCR. In cases with DPT under expression, exonic regions of the DPT gene were sequenced using the Sanger method.
Results: In array samples, DPT expression was decreased in 82.9% (34/41), increased in 12.2% (5/41), and had no changes in 4.9% (2/41). DPT was decreased in 14 fresh samples (36.8%), while 12 cases (31.6%) showed overexpression and the others had no changes. DPT expression showed no significant difference among various tumor grades and stages. The frequencies of DPT overexpression were higher in tumors having lymph node involvement (47.7% vs 28%, P=0.59). In 2 cases mutations were detected that may be responsible for decreased expression of DPT.
Conclusion: The similarities between changing patterns of DPT and TGF-β expression in colorectal cancer demonstrate that DPT may act as a pre-receptor component of the TGF-β signaling pathway in colon carcinogenesis.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 24, Issue 4
April 2021
Pages 444-450

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