p27 Protein and Cancers of the Gastrointestinal Tract and Liver

Chetty, Runjan

doi:10.1097/00004836-200307000-00008

Cited by 37 publications

(26 citation statements)

References 38 publications

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“…Loss of p27 KIP1 expression has been reported in a number of human tumor types including HCC and is associated with poor prognosis and tumor aggressiveness (Chetty, 2003). In normal cells, p27 KIP1 is localized in the nucleus, where it binds to and inhibits CDK2, an activator of E2F1, and promotes DNA replication (Sherr and Roberts, 1995).…”

Section: Discussionmentioning

confidence: 99%

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G₀-G₁ in Human Hepatocellular Carcinoma Cells

Wang

Pan

Guh

et al. 2004

J Pharmacol Exp Ther

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This study delineates the antiproliferative activities and in vivo efficacy of YC-1 [3-(5Ј-hydroxymethyl-2Ј-furyl)-1-benzyl indazole] in human hepatocellular carcinoma cells. YC-1 inhibited the growth of HA22T and Hep3B cells in a concentrationdependent manner without significant cytotoxicity. YC-1 induced G 1 phase arrest in the cell cycle, as detected by an increase in the proportion of cells in the G 1 phase using FACScan flow cytometric analysis. It was further shown that cGMP, p42/p44 mitogen-activated protein kinase, or AKT kinase-mediated signaling pathways did not contribute to the YC-1-induced effect. Of note, YC-1 induced a dramatic increase in the expression of cyclin-dependent kinase (CDK)-inhibitory protein, p21 CIP1/WAP1 , and a modest increase in p27 KIP1 . The association of p21 CIP1/WAP1 with CDK2 was markedly increased in cells responsive to YC-1. YC-1 did not modify the expression of cyclin D1, cyclin E, CDK2, or CDK4. In a corollary in vivo study, YC-1 induced dose-dependent inhibition of tumor growth in mice inoculated with HA22T cells. Immunohistochemical analysis revealed an inverse relationship between the staining of p21 CIP1/WAF and the staining of Ki-67, a cell proliferation marker. Based on the results reported herein, we suggest that YC-1 induces cell cycle arrest and inhibits tumor growth both in vitro and in vivo via the up-regulation of p21 CIP1/WAP1 expression in HA22T cells. Because of this, YC-1 is a potential antitumor agent worthy of further investigation.

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Section: Discussionmentioning

confidence: 99%

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G₀-G₁ in Human Hepatocellular Carcinoma Cells

Wang

Pan

Guh

et al. 2004

J Pharmacol Exp Ther

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“…The eukaryotic cell cycle is divided into four phases: the first growth phase (G 1 ), DNA synthesis phase (S), the second growth phase (G 2 ), and mitosis (M; ref. 1). Numerous mitogenic and quiescence-inducing stimuli must converge at certain points to allow a coordinated cellular response that typifies the normal cell cycle.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of p57Kip2 Induces Prostate Cancer in the Mouse

Jin¹,

Lho

Wang³

et al. 2008

Cancer Research

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“…p27 (KIP1) is a cdk inhibitor that binds to cyclin-CDK complexes and facilitates the inhibition of the catalytic activity of cdk, ultimately inducing G 1 cell cycle arrest (20,21). Inactivation of p27 (KIP1) is believed to be a fundamental step in carcinogenesis, and decreased p27 (KIP1) protein expression correlates with poor prognosis in many human malignancies (22,23). Recent studies demonstrated that p27 (KIP1) is expressed at lower levels in normal hepatocytes (24).…”

Section: Introductionmentioning

confidence: 99%

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

Claudio

Russo

Kumar

et al. 2004

Clinical Cancer Research

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Hepatocarcinoma (HCC) is the fifth most common cancer, with more than one million fatalities occurring annually worldwide. Multiple risk factors are associated with HCC disease etiology, the highest incidence being in patients with chronic hepatitis B virus and hepatitis C virus, although other factors such as genetic makeup and environmental exposure are involved. Multiple genetic alterations including the activation of oncogenes and inactivation of tumor suppressor genes are required for malignancy in human cancers and are correlated with increased stages of carcinogenesis and further tumor progression. In this study of 21 HCC patients, we analyzed pRb2/p130, vascular endothelial growth factor (VEGF), p27 (KIP1) , and proliferating cell nuclear antigen as potential HCC molecular biomarkers. In our sample set, we found that p27 (KIP1) was absent. Univariate survival analysis showed that proliferating cell nuclear antigen expression (diffuse staining >50% of positive cells in tumor) was confirmed as a significant HCC prognostic biomarker for determining patient survival agreeing with previous studies (P ‫؍‬ 0.0126, log-rank test). Lower pRb2/p130 expression was associated to a borderline P value of inverse correlation with tumor malignancy and to a positive correlation with respect to the time from HCC diagnosis (Spearman coefficient ‫؍‬ 0.568; P < 0.05). Conversely, higher VEGF expression was associated with a poor survival (P ‫؍‬ 0.0257, log-rank test). We demonstrate for the first time that pRb2/p130 is inversely correlated with VEGF expression and tumor aggressiveness (P < 0.05) in p27 (KIP1) -negative HCC patients. pRb2/p130 and VEGF expression are independent from tumor staging, suggesting their possible role as independent prognostic molecular biomarkers in HCC. Furthermore, we have evidence that VEGF together with pRb2/p130 may act as new HCC biomarkers in a p27 (KIP1) -independent manner. Additional studies with larger numbers of patient data would allow the use of multivariable techniques and would be able to further identify patients with poorer survival.

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p27 Protein and Cancers of the Gastrointestinal Tract and Liver

Abstract: Therefore, in gastrointestinal and hepatic cancers, low p27 expression is regarded as an important adverse prognostic factor.

Cited by 37 publications

References 38 publications

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G₀-G₁ in Human Hepatocellular Carcinoma Cells

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G₀-G₁ in Human Hepatocellular Carcinoma Cells

Down-regulation of p57Kip2 Induces Prostate Cancer in the Mouse

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

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p27 Protein and Cancers of the Gastrointestinal Tract and Liver

Abstract: Therefore, in gastrointestinal and hepatic cancers, low p27 expression is regarded as an important adverse prognostic factor.

Cited by 37 publications

References 38 publications

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G0-G1 in Human Hepatocellular Carcinoma Cells

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G0-G1 in Human Hepatocellular Carcinoma Cells

Down-regulation of p57Kip2 Induces Prostate Cancer in the Mouse

pRb2/p130, Vascular Endothelial Growth Factor, p27(KIP1), and Proliferating Cell Nuclear Antigen Expression in Hepatocellular Carcinoma

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YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G₀-G₁ in Human Hepatocellular Carcinoma Cells

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Exhibits a Novel Antiproliferative Effect and Arrests the Cell Cycle in G₀-G₁ in Human Hepatocellular Carcinoma Cells