Expression of p57^kip2and its relationship with clinicopathology, PCNA and p53 in primary hepatocellular carcinoma

Abstract

AIM:To investigate the expression of p57 kip2 and its relationship with clinicopathology, PCNA and p53 in primary hepatocellular carcinoma (HCC). METHODS:Expression of p57 kip2 , PCNA and p53 in tumor tissues from 32 patients with HCC and 10 liver tissues of normal persons was detected with Elivision immunohistochemical technique. RESULTS:The p57 kip2 protein positive-expression rate in HCC was 56.25%, lower than that in normal tissues (100%, P<0.05). The reduced expression of p57 kip2 protein correlated significantly with moderate or low differentiation of tumor cells (P = 0.007 <0.05), high clinical stage (P = 0.041 <0.05) and poor prognosis (P = 0.036 <0.05), but did not correlate significantly with metastasis, tumor size, level of AFP and age (P>0.05). The PCNA positiveexpression rate was 56.25%, which was correlated significantly with the expression of p57 kip2 (P = 0.025<0.05). The p53 positive-expression rate was 46.88%, which was not correlated significantly with the expression of p57 kip2 (P>0.05). CONCLUSION:There is a marked loss or absence of p57 kip2 expression and high expression of PCNA in HCC, which are involved in carcinogenesis and development of HCC. The p57 kip2 and p53 may induce apoptosis via different mechanisms.

MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma

“…Our data, in line with those reported in the literature (Ito et al, 2001;Nan et al, 2005), show that CDKN1C/ p57 is downregulated in more than 80% of HCCs, indicating the existence of more than one mechanism affecting CDKN1C/p57 expression in HCC. In this article we describe miR-221 as a direct regulator of CDKN1C/p57 expression in HCC, showing a new mechanism responsible for CDKN1C/p57 downregulation in HCC.…”

“…Notably, loss of CDKN1C/p57 protein expression in HCC tissue was associated with a higher aggressiveness, worse outcomes and lower disease-free survival (Nakai et al, 2002). CDKN1C/p57 downregulation in HCC tissues has also been intimately associated with PCNA overexpression, indicating an increased proliferating activity and a poorer prognosis (Nan et al, 2005).…”

“…These findings, together with those previously reported on CDKN1B/p27 modulation by miR-221, further outline the importance of this miRNA in liver carcinogenesis. Both CDKN1C/p57 and CDKN1B/p27 were previously described as involved in HCC development and as biomarkers of poor prognosis in HCC (Hui et al, 1998;Nan et al, 2004Nan et al, , 2005. The identification of a common regulator of both these CDKIs is, therefore, of great potential relevance, as its modulation might deeply impact deregulation of cell cycle, affecting both CDKN1B/p27 and CDKN1C/ p57 proteins.…”

The Cdk inhibitor p57Kip2 controls LIM-kinase 1 activity and regulates actin cytoskeleton dynamics

“…, most probably because of its Cdk inhibitory function, is frequently considered as a nuclear protein; however, cytoplasmic expression of this protein has been demonstrated in various tissue, tumors and derived cell lines (www.proteinatlas.org; Barbe et al, 2008;Nan et al, 2005;Matsumoto et al, 2000;Pateras et al, 2006;Bozdogan et al, 2008;Joseph et al, 2009). In fact, as for the other members of the family, p21…”

p57: A multifunctional protein in cancer (Review)

“…In the past, p57 was considered to express in the nucleus, however, cytoplasmic expression of this protein has been demonstrated in various tissue, tumors and derived cell lines (15)(16)(17)(18)(19)(20). A p57 expression construct missing the carboxylterminus (amino acid 281) leads to the cytoplasmic localization of p57 and its exclusion from the nucleus (2).…”