The Mechanisms Of The RECK Gene On The Development And Metastasis Of The Prostate Carcinoma

Prostate carcinoma (PCa) is one of the most common malignances among theurological neoplasms and the incidence of PCa is getting higher and higher in Chinatoday with the aging and the diet habit changing. However, the patients with PCa inChina is quite different from that in the western countries, for example, Chinesepatients are often diagnosed as the advanced PCa in the outpatient department whohave lost the opportunity of radical surgery ,which leads to the poor prognosis. Forthose patients, how to inhibit the invasiveness and metastasis of the tumor is of themost importance. So a lot of studies have focused on this field. As known, it is quite complicated for the process of the invasiveness andmetastasis of the malignancies, during which the tumor cells penetrate from the ECMbarrier, break through the basement membrane of the vessels and at last set down in anew suitable area. Previous research showed that the invasiveness and metastasisability of malignances was close related to the amount of the proteinase induced bythe tumor cells, among which the Matrix metalloproteinases (MMPs) were the mostimportant elements. However, the MMP inhibitors were also found to play animportant role in the invasiveness and metastasis of the tumor by balancing the ECMdegradation and remodeling together with the MMPs. Recent studies have shown thatvarious synthized MMP inhibitors contribute to the inhibition of the vessel formationand tumor metastasis. So the study of MMPs and their inhibitors has become apromising field in the tumor invasiveness and metastasis. RECK gene is a new MMP inhibitor which is able to inhibit such three MMPs asMMP-2,MMP-9 and MT1-MMP at least. It has been found that the RECK gene islocated at the 9p13-p12 with a transcript of 4.6kb, and encodes 971 amino acids (MW110kDa) which shares 93% homology with the mouse RECK gene. Until present,little is known about the exact function of the RECK gene. However, some research - 5 -第二军医大学博士论文 RECK 基因在前列腺癌发生和转移中作用机制的研究have shown that the expression level of RECK gene in many kinds of normal tissuesis pretty high, while it is much lower in various kinds of the malignance tissues.Furthermore, the expression level of RECK gene has been found to be negativelyrelated to the invasiveness and metastasis of the tumor. So it is postulated that RECKis a kind of tumor suppression gene which acts by inhibiting the expression of theMMPs. Besides, the RECK gene has been found to be regulated by some agents suchas Nonsteroidal nati-inflammatory drugs (NSAIDs). Previous research believed thatNSAIDs was able to inhibit the progression and metastasis of the tumor probably bysuppressing the Cyclooxygenase (COX) activity. But recent studies have shown thatNS398 was able to increase the expression of the RECK gene, instead of suppressingthe COX activity to inhibit the metastasis of the tumors. Some studies have shown that in the liver and pancreas carcinoma tissues, theexpression of the RECK gene is negatively related to the invasiveness and metastasisof the tumors, implicating that RECK gene may become a promising molecule markerto predict the prognosis in those kinds of the tumors. To the best of our knowledge therelationship between Reck and MMPs in prostate cancer has not previously been documented Our study aimed to find out the relationship between the RECK gene and the PCafrom the following four aspects: the expression of RECK gene in the PCa tissues, theexpression of RECK gene in various prostate cell strains, NS398 stimulation test oncell strain(DU-145) and the NS398 stimulation test on the PCa animal model. First,using the technique of the RT-PCR and Real-time PCR, we found that the expressionof the RECK gene in the PCa tissues was much lower than that in the normal prostatetissues, while the expression of the MMP-2 and MMP-9 was much higher in the PCatissues tha...