Divergent expression patterns of SATB1 mRNA and SATB1 protein in colorectal cancer and normal tissues.

Anna E Kowalczyk,Piotr Dziegiel,Bartlomiej E Krazinski,Jolanta Kiewisz,Janusz Godlewski,Jacek Janiszewski,Zbigniew Kmiec,Agnieszka Sliwinska-Jewsiewicka,Przemyslaw Kwiatkowski,Bartosz Pula,Piotr M Wierzbicki

doi:10.1007/s13277-015-3084-0

Abstract

Special AT-rich sequence-binding protein 1 (SATB1) is a ‘genome organizer,’ and it has been proposed as a factor that affects the development and progression of various human neoplasms, including colorectal cancer (CRC). This study aimed to compare SATB1 expression in a group of CRC patients and healthy subjects at the mRNA and protein levels. We collected paired tumor tissue and unchanged mucosa of the large intestine from 102 CRC patients as well as 53 biopsies of normal colon mucosa obtained from healthy patients during screening colonoscopy. Tissue samples were quantified for SATB1 mRNA by quantitative PCR, while SATB1 protein expression was determined by Western blotting and immunohistochemistry. SATB1 mRNA level in tumor tissues was over twofolds lower than in samples of corresponding unchanged tissues and fourfolds lower than in biopsies of healthy colon mucosa. Western blotting analysis revealed that SATB1 protein content in tumor and unchanged tissues of CRC patients was over sixfold and fivefolds higher than in biopsies of healthy colon mucosa, respectively. Immunohistochemical staining demonstrated higher nuclear and cytoplasmic SATB1 reactivity in the tumor tissue compared to unchanged mucosa of CRC patients. Despite these differences, SATB1 mRNA, protein, and immunoreactivity levels did not correlate with patients’ clinicopathological data and their overall survival, but the latter analysis was limited by a relatively short period of follow-up. In conclusion, we suggest that some as yet unidentified posttranscriptional mechanisms that regulate SATB1 expression may be altered in the CRC tissue.

Highlights

Colorectal cancer (CRC) is the third most commonly diagnosed cancer accounting for about 10 % of total adult malignancies worldwide
To determine the expression of SATB1 at the mRNA level, matched tumor and unchanged tissues derived from CRC patients and colonic biopsies of healthy group were subjected to quantitative PCR (qPCR) analysis
SATB1 has been proposed as an important factor that controls the development and progression of various human neoplasms [10]; its role in cancer pathogenesis has yet not been fully elucidated

Summary

Introduction

Colorectal cancer (CRC) is the third most commonly diagnosed cancer accounting for about 10 % of total adult malignancies worldwide. SATB1 can influence the expression of more than 1000 genes, including those implicated in the pathogenesis of human neoplasms [3] This protein may play a role in breast cancer cell proliferation [4] and was found to be upregulated in several malignancies such as breast, laryngeal, gastric, liver, and ovarian cancers [3, 5,6,7,8]. Results of many studies suggest that SATB1 overexpression is associated with an aggressive phenotype of tumor cells. The expression level of SATB1 correlated with cancer progression and was suggested to be an useful prognostic marker in breast cancer, laryngeal squamous cell carcinoma, cutaneous melanoma, glioma, gastric, and hepatocellular cancer [3, 5,6,7, 10]. The reports suggest that SATB1 can be expressed in a tissue-typical manner, and prognostic value of SATB1 may be cancer-type specific; contradictory results could be observed even in the same tumor type

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