Decreased expression of p73 in colorectal cancer

Abstract

Introduction. The colorectal cancer (CRC) is one of the most frequent cancer in Poland and worldwide. This disease is characterized by distinct genetic alterations. p73 belongs to the p53 gene family; however, its role in the pathogenesis of CRC has not been completely understood. p73 gene encodes several mRNA variants and protein isoforms with its longest and fully functional p73a (mRNA) and TAp73a (protein) isoform. The aim of the study was to investigate p73 gene expression at the mRNA (p73a) and protein (TAp73a) levels in CRC. Material and methods. Small sections of the CRC tumor tissue and macroscopically unchanged colon mucosa and submucosa from the dissection margin were collected from 23 patients diagnosed with CRC. p73 mRNA levels were measured by Real-time PCR (QPCR) method and the expression level of TAp73a protein was assessed by Western blotting (WB) and immunohistochemical (IHC) staining. Results. We found a 37% decrease in the level of p73a mRNA in neoplastically changed (tumor) compared with unchanged normal colon tissue from the surgical margin (p = 0.041). No correlations were found between mRNA levels in cancer tissue and clinical-pathological parameters. The semi-quantification of TAp73a protein revealed lower and higher TAp73a protein contents in 11/23 and 12/23 of tumor samples, respectively, when compared with the median value of TAp73a protein in normal colon tissue (p = 0.61). The level of TAp73a protein level was 5 times lower in poorly differentiated cancer cells (G3) in comparison to moderately differentiated ones (G2; p = 0.02). No statistically significant correlations were observed between the level of the TAp73a protein and clinical-pathological patients' characteristics. The IHC analysis of TAp73a protein presence in CRC samples showed decreased immunoreactivity when compared with matched sections of the unchanged colon wall in 4/9 patients, similar intensity of the IHC reaction in 4/9 patients and increased immunoreactivity in 1/9 patients. The TAp73a protein was localized mainly in the cytoplasm of the cancer cells. No statistically significant correlations between IHC results and clinical-pathological features of the patients were found. Conclusions. The obtained results suggest that the p73 gene may play a role as a tumor suppressor in the CRC progression.

p73 – NAV3 axis plays a critical role in suppression of colon cancer metastasis

“…A recent study assessed the expression of p73 gene in tumor-surgical margin specimens of CRC patients at the mRNA and protein levels and found decreased expression of p73 in CRC tumor tissue as compared to unchanged colon mucosa 16 . In line with these results, we wanted to compare the expression of NAV3 and p73 by IHC in metastatic and non-metastatic colon cancer tissues and determine whether there is co-expression of NAV3 and p73 as implicated in our studies.…”

“…It has been shown that TA-p73 null mice are prone to lung cancer, indicating that it functions as a tumor suppressor [13][14][15] . Moreover, a recent study revealed a 37% decrease in the levels of TAp73 mRNA in neoplastic tissue as compared to that of normal colon tissue, suggesting that p73 may play a role as a tumor suppressor in colorectal cancer (CRC) progression 16 . In addition to pro-arrest and pro-apoptotic roles, p73 also exerts its tumor suppressor function by suppressing metastasis 17 .…”

TP73 is a credible biomarker for predicting clinical progression and prognosis in cervical cancer patients

“…Zhang et al [38] demonstrated metastatic melanoma tissues exhibited high TP73 expression in comparison with primary melanoma tissues. However, there was no statistical association between TP73 expression and clinicopathologic features in hepatocellular carcinoma [39], colorectal cancer [25,40,41] and ovarian cancer [42]. Generally, the clinical significance of TP73 expression had obvious difference depending on the type of human cancers.…”

Case-control Study on p73 rs1801173 C > T Gene Polymorphism and Susceptibility to Gastric Cancer in a Chinese Han Population

“…Recent studies have demonstrated that a high number of genes and various environmental factors are the causal agents of GC, and the presence of different forms of alleles in gene polymorphisms may promote the development of cancers. In this regard, p73 has been a research focus due to its role as a major tumor suppressor gene [27] . p73 has some functions similar to or independent of p53 and plays a role, particularly in compensation for loss of p53 function, in the regulation of cell cycle, DNA repair, apoptosis, and possibly cell differentiation.…”