Zhu et al. Journal of Experimental & Clinical Cancer Research 2010, 29:124 http://www.jeccr.com/content/29/1/124 Page 7 of 8 and integrity, is present in germ cells, proliferative gran- ulose cells, germline stem cells, and neoplastic cells in the ovary, but is absent from differentiated or aged cells. Activation of telomerase in the ovary underpins both benign and malignant cell proliferation. Normally, high levels of telomerase activity are a hallmark of cancer, including ovarian epithelial carcinoma [21]. Accumulat- ing data indicate that telomerase activation is an early event in ovarian carcinogenesis [22-25]. As expected, the telomerase activities were positive in both SKOV-3 and ES-2 cells and negative in HUVECs. At the same time, the telomerase activities in ELs from SKOV-3 cells with or without Sirolimus treatment were also positive while those in ELs from ES-2 cells with or without Siro- limus were negative. The difference of telomerase activ- ity between the two ELs may contribute to the different proliferative behaviors of the two cells. To explore the underlying mechanisms of the SKOV-3 and ES-2 changed to ELs by hypoxia treatment, we detected the expression of some relative genes in the SKOV-3, ES-2, SKOV-3 ELs, ES-2 ELs, with or without Sirolimus, and HUVECs. As Fig. 3 shown, compared with the original cancer cells, the ELs represented the elevated HIF-1a, VEGF, VEGF receptor-2 (Flk-1) and p53 mRNA expression, while the expression of Cyclin D1 was decreased. Our and others’ studies have indi- cated that HIF-1a played a vital role for the angiogen- esis and VM under hypoxia [11,26-28]. To determine the origin of the change in VEGF and Flk-1 expression, we used the Sirolimus to inhibit the activity of HIF-1a. Sirolmus, known as rapamycin, is proved to be as the inhibitor of HIF-1a [26,29,30]. Consistent with other researches, the changes in the expression of VEGF, Flk- 1 and Cyclin D1 were HIF-1a transcriptional dependent [10,31]. However, the change in the expression of p53 was HIF-1a transcriptional independent. Conclusion In summary, the ovarian cancer cells could be induced into ELs which seemed similarly to progenitor endothe- lial cells by hypoxia. After induced, the ELs would get some characteristics of endothelial cells and would lose some malignant characteristics of the original cancer cells. The increased expression of HIF-1a, and HIF-1a depended VEGF and Flk-1 might contribute to the VM and the vasculogenesis. During the transition, HIF-1a took an important role in the molecular mechanisms, while there still has other HIF-1a-independent mechan- ism in this process. List of abbreviations EL(s): endothelial-like cell(s); EOC: epithelial ovarian cancer; EVA: ethylene vinyl acetate; HIF-1: hypoxia-inducible factor-1; HUVEC: human umbilical vein endothelial cell; LCM: laser capture microdissection; RT-PCR: reverse transcription polymerase chain reaction; TRAP-ELISA: telomerase repeat sequence amplification-enzyme linked immunosorbent assay; VEGF: vascular endothelial growth factor. Competing interests The authors declare that they have no competing interests. Authors’ contributions PZ carried out the proliferation, cell cycle and apoptosis assay, participated in drafted the manuscript. YN carried out the invasion experiment, participated in experiment design and drafted the manuscript. LY conceived of the study, participated in its design and coordination, performed the statistical analysis and helped to draft the manuscript. MC carried out the telomerase activity assay, participated in the draft preparation. CX participated in the design of the study and performed the statistical analysis. All authors read and approved the final manuscript. Authors’ informations PZ, M.D., medical master candidate, Dept. Gynecology, Obstetrics & Gynecology Hospital, Fudan University; senior medical registrar, Dept. Obstetric & Gynecology, Shangyu City Hospital; YN, M.D. & Ph.D., assistant professor, Dept. Physiology & Pathophysiology, Shanghai Medical College, Fudan University; LY, M.D. & Ph.D., associate professor & medical consultant, Dept. Gynecology, Obstetrics & Gynecology Hospital, Fudan University; MC, M.B., medical master candidate, Dept. Gynecology, Obstetrics & Gynecology Hospital, Fudan University; CX, M.D. & Ph.D., professor & senior medical consultant, Dept. Gynecology, Obstetrics & Gynecology Hospital, Fudan University. Acknowledgements This study was supported by National Natural Science Foundation of China grants 30471806, 30470689 and 30900716, Postdoctoral Science Foundation of China grant 20040350454, and Science and Technology Commission of Shanghai Municipalitygrant 04JC14021. Author details 1Department of Gynecology, Obstetrics & Gynecology Hospital, Fudan University, 419 Fangxie Rd, Shanghai, 200011, China. 2Department of Obstetric & Gynecology, Shangyu City Hospital, 517 Shimin Blvd Baiguan St, Shangyu, Zhejiang Province, 312000, China. 3Department of Physiology & Pathophysiology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China. Received: 24 August 2010 Accepted: 10 September 2010 Published: 10 September 2010 References 1. 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