Expression of the cdc25B gene as a prognosis marker in non-small cell lung cancer
Introduction
The most important determinant of prognosis in non-small cell lung cancer (NSCLC) is the stage of disease [1]. However, a significant number of tumors at early-stage show aggressive behavior and a tendency to relapse. It was reported that micrometastastic cancer cells were present in the bone marrow of patients with resectable early-stage NSCLC [2]. Moreover, the prognosis for patients with operable NSCLC remains gloomy in comparison with that observed in gastric, colon, or breast cancer operable tumors [3]. Despite steadily accumulating evidence that numerous genetic markers influence the biologic behavior of NSCLC [4], the intrinsic nature of gene dysregulation that leads small tumors to metastasize remains highly elusive [5].
cdc25s can dephosphorylate threonine 14, tyrosine 15, or both on CDKs and activate cyclin/ CDK complexes to stimulate cell proliferation. It has been suggested that cdc25A and cdc25B but not cdc25C possess oncogenic properties [6]. Because myc-family may induce expression of cdc25A and cdc25B [7], it was reported that cdc25B overexpression in non-Hodgkin's lymphoma might cooperate with c-myc oncogene [8]. Recent studies showed that overexpression of cdc25B was frequent and as a poor prignostic marker in colon cancer [9].
As available prognostic markers leave much to be desired for NSCLC, we investigated cdc25B transcript in patients with NSCLC by means of a reverse transcription polymerase chain reaction (RT-PCR) analysis using LightCycler [10]. And we analyzed the data in reference to the clinicopathological factors and prognosis.
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Patients
The study groups included 55 NSCLC patients who had undergone surgery at the Department of Surgery II, Nagoya City University Medical School between January 1997 and December 1999. The lung cancers were classified according to the general rule for clinical and pathological record of lung cancer [11]. All tumor and normal lung samples were collected at resection and immediately frozen in liquid nitrogen.
The clinical and pathological characteristics of the 55 NSCLS patients are shown in Table 1;
cdc25B protein expression
Of 37 NSCLC tissue samples tested, 26 tissue sections were positive for cdc25B immunostaining. Positive staining was seen in the cytoplasm of a fraction of tumor cells. Normal lung alveolar cells and parenchyma were not stained (Fig. 1). The cdc25B immunostaining was correlated with cdc25B mRNA expression (Table 1).
cdc25B mRNA expression
Of 55 NSCLCs studied, the relationship between the cdc25B expression in NSCLC and the patients’ clinicopathological factors is shown in Table 1. There was no difference of cdc25B
Discussion
In the present study, cdc25B mRNA expression was analyzed in NSCLC using LightCycler. There was no difference of cdc25B/GAPDH gene expression level between NSCLC tissue and normal lung tissue. In fact, only 22/55 (40%) of NSCLC overexpressed cdc25B transcript. c-myc is overexpressed in about 30% of NSCLC [12]. Thus majority of NSCLC case is not related with increased myc-cdc25 pathway.
cdc25 genes are a family of cell cycle-activating phosphatases [13]. These phosphatases act at different points
Acknowledgements
The authors would like to thank Mrs Miyazaki for her excellent technical assistance.
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