| Background Tumors are considered to be a multi-gene disorders, activation of oncogenes and inactivation of tumor suppressor genes are considered as the key factors for the development of tumors. Identification of the cancer-related genes and definition of their involvement in the pathogenesis of malignant tumors are the basis for cancer treatment individualization and new treatment programs target. Due to lack of early diagnosis methods, ovarian cancer is the most deadly gynecologic malignancy in the tumor types. Although in recent years, the improvement of surgical techniques which can be done maximum cytoreductive surgery and the clinical application of Platinum, Taxol, and many second-line chemotherapy which bring multi-vitality to chemotherapy, the prognosis of patients with ovarian cancer had improved little, its five-year survival rate is still hovering around 30%. Therefore, the further elaboration of the mechanisms of ovarian cancer occurrence and development, so as to fundamentally reduce ovarian cancer mortality, is today the one of the important research directions of ovarian cancer research. In Drosophila, lethal giant larvae (Lgl) has been proven to be a tumor suppressor gene. Lgl is an evolutionarily conserved molecule that functions linking cell polarity regulation to cell proliferation control in the epithelial tissues. The human gene Hugl-1 has significant homology to the Drosophila tumor suppressor Lgl. The human protein, Hugl-1, contains several conserved functional domains found in Lgl including homo-oligomerization domains, a cluster of phosphorylation sites, at least two WD-40 repeats suggesting these proteins may have closely related functions. The atypical protein kinase C (aPKC) proteins are a subgroup of the PKC family of serine-threonine protein kinases that comprise theι/λandζisoforms in mammals. These proteins belong to the evolutionarily conserved PAR apical complex and are involved in the determination of the apical dentity both in the invertebrate and vertebrate epithelial cells Studies have shown that overexpression of aPKC takes effect in cell proliferation, cell migration, as well as invasiveness. These results suggested that aPKC should be an oncogene. Both in invertebrate and mammals it has been demonstrated that, when aPKC is found in an active apical PAR complex, it is able to phosphorylate Lgl inducing its detachment from the plasma membrane owing to a conformational change. This displacement results in an Lgl inhibition at the apical domain. Lgl, in turn, inhibits aPKC function at the basolateral domain, probably recruiting a still unknown PAR antagonist or sequestering aPKC in an inactive complex at that region. This mechanism of mutual exclusion plays a fundamental role in the epithelial structure; when disrupted, cells indeed fail to maintain the correct shape and over-proliferate, as can be observed upon Lgl depletion or aPKC ectopic expression.Objective The aim of this study is to assess the expression of Hugl-1 and aPKC in primary serous ovarian carcinoma and to analyze the correlation of the expression level of Hugl-1 and aPKC. At the same time, this study aims to correlate the results of immunohistochemical analysis with various clinicopathologic parameters, which to discover the roles of Hugl-1 and aPKC in the development of serous ovarian carcinoma.Materials and Methods: The subject of this study is 79 patients diagnosed of serous ovarian cancer and undergone operations. The control team includes 25 cases of normal ovarian epithelial tissues, 31 cases of serous ovarian benign tumor tissues and 41 serous ovarian borderline tumor tissues, which collected in the same time as the serous ovarian cancer tissues. The expressions of Hugl-1 and aPKC in these cases were detected by immunohistochemical S-P method. Also we analyzed the relationship between the expression of Hugl-1/aPKC and the clinicopathological parameters of the ovarian cancer patients.Results Positive expressions of Hugl-1 in normal, benign, borderline and serous ovarian cancers were88% ( 22/25 ),96% ( 30/31 ),96% ( 30/31 ) and 51% ( 40/79 ) respectively. The expressions of Hugl-1 in serous ovarian cancers were significantly lower than those in normal, benign and borderline tissues ( P < 0.05 ) .The expressions of aPKC in normal, benign, borderline and serous ovarian cancers were 12% ( 3/25 ),19% ( 6/31 ),32% ( 13/41 ) and 63% ( 50/79 ) respectively. The expressions of aPKC in serous ovarian cancers were significantly higher than those in other groups( P < 0.05 ). The expressions of Hugl-1 and aPKC were respectively related to pathological grade, FIGO stage and Lymph node metastasis. There wasn't correlation between the expressions of the two proteins in serous ovarian cancer ( P > 0.05 ) .Conclusion 1 .Compared with normal OSE, the expression of Hugl-1 in serous ovarian cancer tissues was low, and the expression of aPKC was high. These results suggest that Hugl-1 and aPKC may be involved in the occurrence and development of serous ovarian cancer.2.The expressions of Hugl-1 and aPKC in serous ovarian cancer tissues were linked to FIGO stage, histological grade and Lymph node metastasis. These results suggest that Hugl-1 and aPKC may be related to poor prognosis of serous ovarian cancer.
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