Cancer Letters

Cancer Letters

Volume 276, Issue 1, 8 April 2009, Pages 88-94
Cancer Letters

CIAPIN1 inhibits the growth and proliferation of clear cell renal cell carcinoma

https://doi.org/10.1016/j.canlet.2008.10.044Get rights and content

Abstract

Our previous studies indicated a direct correlation with loss of CIAPIN1 and carcinogenesis of tumor in human gastric cancer. Here we presented that the expression of CIAPIN1 was absent or significantly decreased in 102 cases of clear cell renal cell carcinoma (CCRCC) tissues (P < 0.05). Up-regulating CIAPIN1 by adenoviral vectors exhibited significant inhibition of CCRCC-derived cell growth in vitro and in vivo with G1 cell cycle arrest. Simultaneously, CIAPIN1-induced growth suppression was found partially to regulate various proteins, including inhibition of cyclinD1, cyclinE, cdk2, cdk4, p-Rb and VEGF, but up-regulation of p27Kip1 and Rb.

Introduction

Renal cell carcinoma (RCC) accounts for 2–3% of all malignant tumors in adults, which afflicts about 150,000 people globally and accounts for nearly 78,000 deaths each year [1]. Clear cell RCC (CCRCC), originated from proximal tubule cells, is the most common pathological type of renal cancer. Although several genes have been found to be involved in carcinogenesis of CCRCC, more great efforts are needed to identify new genes which are responsible for the process.

CIAPIN1, originally named anamorsin or V62, is a gene cloned recently and has been found to protect cells from etoposide, γ-radiation, staurosporine, and cytokine withdrawal [2]. Previous studies by our laboratory indicated a direct correlation with loss of CIAPIN1 and proliferation of tumor in human digestive cancer, which indicated that CIAPIN1 could be an important molecule involved in carcinogenesis [3], [4], [5]. In this study, the expression and effects of CIAPIN1 on CCRCC were investigated.

Section snippets

Tissue collection and immunohistochemistry

Immunohistochemistry was performed using the Histostain™-Plus SP kit [6]. Formalinfixed paraffin-embedded specimens (102) of primary CCRCC and the matched adjacent noncancerous tissues were obtained from the Department of pathology in our hospital. Ten resected fresh CCRCC and adjacent non-tumorous specimens were collected in the Department of Urology in our hospital and were immediately frozen in liquid nitrogen and kept at −70 °C until the extraction of lysate. All samples were obtained from

CIAPIN1 expression was decreased or absent in CCRCC

The expression of CIAPIN1 was assessed by immunohistochemistry in 102 CCRCC samples with the matched adjacent noncancerous tissues. It was found that CIAPIN1 was predominantly located in the cytoplasm and membrane of kidney proximal tubular cells (Fig. 1). As shown in Table 1, CIAPIN1 positive expression in CCRCC was 37.25% (38/102), significantly lower than 84.31% (86/102) in the non-tumor adjacent tissue (P < 0.01). The average staining score in adjacent noncancerous tissue of CCRCC was

Discussion

Renal cell carcinoma (RCC) remains a clinical challenge due to its complicated pathogenesis. In these cases, the majority (75%) are clear cell RCC [17]. Although a number of cellular genes have been identified to be involved in CCRCC, greater efforts are needed to identify more proteins specifically related to CCRCC carcinogenesis, which may develop new markers for the diagnosis and new targets for therapy. We presented the first evidence that CIAPIN1 gene was significantly lowly expressed in

Conflict of interest

No conflict of interest exits in the submission of this manuscript.

Acknowledgement

We thank Dr. Harold Lovvorn (Dept. of Pediatric Surgery, Vanderbilt University Children’s Hospital) generously provided critic reading of manuscript. This study was supported in part by grants from the National Scientific Foundation of China (30801330).

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    These authors contributed equally to this work.

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