Study of different biochemical markers: bikunin, follistatin and activin significance in different types of ovarian cancer | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 11, Volume 26, Issue 1, June 2006, Page 129-148 PDF (213.05 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2006.37439 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
| Gihan Sharara* 1; Samer Zahran2; Mohamed El-Samra3 | ||||
| 1Medical Biochemistry, Faculty of Medicine, Alexandria University | ||||
| 2Medical Biochemistry, Faculty of Medicine, Tanta University | ||||
| 3Obstetrics and Gynecology, Faculty of Medicine, Alexandria University | ||||
| Abstract | ||||
| OVARIAN CANCER HAS the second highest incidence in gynecologicalcancers and is the fifth leading cause of cancer death among women in the world. Characterizing the pathwaysthat regulate the growth of ovarian cells is necessary for understanding the events that lead to development of ovarian cancer. The aim of the present study was to evaluate the potential clinical implication of circulating Activin A, follistatin, bikunin, ovarian tissue urokinase Plasminogen Activator (uPA) and Smad-2 (fusion between Drosophila mothers against dpp (Mad) and C. elegans Sma)expression for diagnosis and progression of ovarian cancer. Subjects: The study was carried out on 75 women divided as follows: 15 women with serous ovarian carcinoma, 15 women with mucinous ovarian carcinoma, 15 women with serous ovarian cystadenoma, 15 fertile healthy women, 15 postmenopausal healthy women. Methods:Serum levels of Activin A and Follistatin, and Plasma levels of Bikunin were estimated using ELISA. Urokinase plasminogen activator (uPA) was extracted from ovarian cancerous tissue and its levels estimated by ELISA. Detection of Smad2 mRNA in ovarian tissue was performed by Reverse Transcription – Polymerase Chain Reaction analysis (RT-PCR). Results: The levels of serum Activin A and Follistatin were found to be significantly higher in serous and mucinous ovarian carcinoma than in ovarian cystadenoma and controls (pre- and postmenopausal). Plasma levels of Bikunin were estimated to be significantly lower in patients with serous ovarian carcinoma and mucinous ovarian carcinoma than in controls and than patients with ovarian cystadenoma. In the present study, levels of uPA in ovarian tissue were significantly higher in serous ovarian carcinoma than in ovarian cystadenoma and controls. Levels of uPA were significantly higher in mucinous ovarian carcinoma than all other groups. Levels of uPA were found to be increased with progression of the stage of ovarian tumor. Correlation studies showed direct positive significant correlations between Activin A and Follistatin, Activin A and uPA, Follistatin and uPA. Also, Bikunin was found to be inversely correlated to Activin A, Follistatin and uPA. Smad-2 expression was detected in 75% of cases of serous ovarian cystadenocarcinoma, in 90% of mucinous ovarian carcinoma. Conclusions:In summary, activin A induces the proliferation of both serous and mucinous ovarian carcinoma. Therefore, activin A may be regarded as both a potentialgrowth factor and a tumor marker. The significantly elevated levels of serum follistatin (Activin – binding protein) in ovarian carcinoma indicated that activin is free and this modulated its signal transduction as illustrated by the expression of Smad-2 in 90% of mucinous ovarian carcinoma and in 75% of serous cystadenocarcinoma. The present study shows that the activin/Smad signaling pathwayis functional in ovarian cancer cells which most probably promotes tumor growth. It is proposed that Smad-2 increased the levels of uPA which is a proteolytic enzyme that enhances tumor growth, progression, invasion and metastases. Plasma bikunin concentration might be a strong and independent favorable prognostic marker for ovarian cancer. It may be concluded that bikunin might attenuate Activin A-elicited signaling cascades in ovarian cancer this probably suppresses uPA expression. Treatment with bikuninmay be beneficial to delay the appearanceof metastatic disease and/or combined with cytotoxic agents toimprove treatment efficacy in advanced ovariancancers. | ||||
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