Ma et al. Journal of Experimental & Clinical Cancer Research 2010, 29:85 http://www.jeccr.com/content/29/1/85 Page 4 of 6 Table 2: Relative content of BMP-2 protein of BMP-2 and its receptors in ovarian tissues Ovarian cancer Benign ovarian tumor Normal ovarian tissue P value BMP-2 0.805 ± 0.105 0.958 ± 0.103 0.975 ± 0.082 0.019 BMPRIA 0.951 ± 0.101 0.911 ± 0.113 1.026 ± 0.099 0.361 BMPRIB 0.816 ± 0.108 0.905 ± 0.115 1.029 ± 0.087 0.042 BMPRII 0.867 ± 0.119 0.974 ± 0.097 1.077 ± 0.103 0.043 with the five-year survival rate of ovarian cancer patients (Table 3). Discussion In 1965, Urist successfully induced heterotopic bone for- mation by grafting decalcified bovine bone into muscles and skin[17]. Accordingly, we conclude that some sub- stance in bone matrix is capable of inducing bone forma- tion, namely BMP. BMP can differentiate mesenchymal cells into osteoblasts, plays various roles during embry- onic development, and is of crucial importance to the nervous system, hematopoietic cells, the heart and liver, etc. BMP cannot act without its receptors, namely, BMPRI (BMPRIA and BMPRIB) and BMPRII, which are located on chromosomes 10q23, 4q22-24, and 2q33-34. BMPRIA mediates growth stimulation signals, and BMPRIB transfers growth inhibition signals[3]. BMPs bind with type II receptors first, after which the type II receptor phosphorylates the type I receptor. The recep- tor-ligand complex phosphorylates the Smad system, and then the complex shifts into the cell nucleus and is involved in gene transcription, thus transferring the BMP signal to the target gene. At present, there are 16 known BMPs, and the majority of research has focused on BMP-2. In 1988, Wozney screened a gene named hBMP-2 from human U-20S cell cDNA based on a bovine BMP amino acid sequence[18]. The hBMP-2 cDNA was 1188 bp in length, encoded 396 Figure 2 The protein expression of BMP-2 and its receptors de- tected by western blot 1: Ovarian cancer tissue; 2: Benign ovarian tumor tissue; 3: Normal ovarian tissue. amino acids, and was located on chromosome 20 in the p21 region. BMP-2 plays an important physiological role in various tissues throughout the body and has been shown to be expressed in tumor tissues. Moreover, its effects vary depending on the tissue. For example, studies have dem- onstrated that BMP-2 and its receptors are expressed in breast cancer[19], colon cancer[15], gastric cancer[20] and that its expression may be associated with the biolog- ical behavior of the tumor. In vitro trials have confirmed that BMP-2 can inhibit the growth of some tumors. Con- versely, other research has suggested that BMP-2 can stimulate the growth of tumor cells in vitro, such as lung cancer[9,10] and prostatic carcinoma[21]. There are only a few reports on the correlation of BMP-2 and ovarian cancer. For instance, Kiyozuka [22] and Le Page [23] both detected the expression of BMP-2 in ovarian cancer tis- sues, and Kiyozuka further confirmed that BMP-2 was involved in the formation of serous ovarian cancer psam- moma bodies. Soda[16] has reported that BMP-2 can inhibit the growth of cancer cell clones in 2 of 15 ovarian cancer patients, but no study has investigated the influ- ence of BMP-2 on prognosis for ovarian cancer patients or the underlying mechanisms behind its role in the development of ovarian cancer. In this study, BMP-2 was shown to be expressed in ovarian cancer, benign ovarian tumors, and normal ovar- ian tissue, and its expression in ovarian cancer was clearly lower than the latter two. This evidence suggests that the BMP-2 gene is likely expressed in normal ovarian tissue, where it acts as a protective factor. Thus, variation or loss of its expression may promote the development of ovar- ian cancer. The BMP-2 receptors BMPRIA, BMPRIB, and BMPRII were also expressed in all three types of tissue, and the expression levels of BMPRIB and BMPRII in ovarian cancer tissue was significantly lower than those in benign ovarian tumors and normal ovarian tissue, although the difference in the BMPRIA expression level between the different tissues was not significant. This suggests that BMP-2 may act through its receptors, BMPRIB and BMPRII, in ovarian cancer. Previous studies have shown that BMPRIA mediates growth stimulation signals, while BMPRIB transfers growth inhibition sig- nals. Our evidence suggests that the weakening of the