Expression Of MRNA Of A₃AR And HIF-1α In Carcinoma Of Large Intestine And Their Clinical Significances

ObjectiveDuring the growth of tumor,because of the quick cell proliferation,tumor microenvironment is all the time in the situation of relative hypoxia that is correlative with biological behaviour of tumor cells,such as growth, differentiation, infiltration, apoptosis and metaptosis.Adenosine is the precurosor and metabolic product of adenine mononucleotide,forming on the condition of cellular oxidation or stress,increasing on the condition of hypoxia and inflammation. Adenosine adjusts many physiological processes by its four membrane receptors: A1AR,A2aAR,A2bAR and A3AR.Among them, A3AR(Adenosine A3 Receptor) plays an inportant part in antiinflaming, immune suppression, inhibiting or enhancing the growth of tumors. The expression of A3AR increases in inflammatory and tumor cells,it is hoped to be an significant biological parameter of diagnosis of diseases. HIF-1 (Hypoxia-inducible factor-1) regulates the process of angiogenesis,erythrocytopoiesis,et al,by ranscriptional activation of target genes under the condition of hypoxia. HIF-1αis the subunit of HIF-1,and decide its activity.The relation of HIF-1αto the growth,invasion and metastasis of tumor cells is especially noticed.Some studies reveal that in tumor tissues,the up-regulation of the expression of A3AR can activate the hypoxia-inducible way such as P42/P44 and P38MAPKs,AKT,etal, which can up-regulate the expression of HIF-1αand induce angiogenesis of tumors and immigration of tumor cells.By detecting the expression of A3ARmRNA and HIF-1αmRNA,my study will discuss the relation between the two genes and clinical and pathological parameter of the carcinoma of large intestine,and their dependablity of the two genes. MethodsFrom May to October ,2008,26 patients with carcinoma of large intestine which were confirmed in pathological way and did not run radiotherapy or chemothera- py, from jinan No.4 People's Hospotal,China,were initially regarded as potential candidates for our study.All specimens were properly treated after obtained by coloscopy or operation.Expressions of A3AR and HIF-1αin these specimens and and their corresponding latero-carcinoma tissues were detected by methods of real-time RT-PCR, and their correlation with characteristics of clinical materials were evaluated.ResultsReal-time RT-PCR revealed:The high expression of A3AR(t=2.815,P<0.05) in carcinoma of large intestine and was correlated with the lymph node metastasis and the clinical stages(t=2.611,P<0.05;t=2.108,P<0.05) ;The high expression of HIF-1α(t=3.912,P<0.05) was found in the carcinoma of large intestine and was correlated with the lymph node metastasis and the clinical stages (t=2.237,P<0.05;t=2.969,P<0.05).;The expression of mRNA of A3AR and HIF-1αis to have nothing to do with sex,age,site and pathological stages.There was no obvious correlation between the expression of A3AR and HIF-1αin adenocarcinoma of large intestine (r= 0.0633,P>0.05).ConclusionsThe expression of A3AR and HIF-1αmRNA in carcinoma of large intestine was high and both closely related to the lymph node metastasis and the clinical stages of carcinoma of large intestine, The detection for these two genes may be useful to the study of the growth,invasion and metastasis of carcinoma of large intestine. The two genes are hoped to become the significant biological parameters of diagnosis of malignancy degree of carcinoma of large intestine.