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Kallikrein 6 Expression, Regulation In Ovarian Cancer And The Clinical Role

Posted on:2008-08-02Degree:MasterType:Thesis
Country:ChinaCandidate:F ZhangFull Text:PDF
GTID:2144360212493896Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
[OBJECTIVE] Ovarian cancer is one of the common malignant tumors in thedepartment of gynecology. Because of the onste delitescence and the lack of tumor markers for early diagnosis, now ovarian cancer is threatening the women's health seriously. At present, the pathogenesis of ovarian cancer is still unknown. The epidemiologic study shows that the risk factors for ovarian cancer include the endocrine factor, the hereditary factor, the bad eating habit and so on.. The search for tumor markers for the early detection and outcome prediction of ovarian carcinoma is one of the critical subjects in the study of ovarian cancer. Meanwhile,it is the key to decrease the fatality rate of the patients to find out the the pathogenesis of ovarian cancer and the role of the cancer associated genes by the latest molecular biology techniques. Human tissue kallikrein(KLK) gene family is one lately discovered tumor markers family that associated with the steroid hormone. KLK6 gene is one member of this family and encodes for human kallikrein 6 (hK6). The hK6 protein, a trypsin-like serine protease,consists of 223 amino acids and is closely related with ovarain cancer. One of the purpose for this reseach is to initially approach the role of KLK6 gene during the development of ovarian cancer by the estrogen regulation test. The other is to find a new tumor marker for ovarian cancer by examining the expression of hK6 in the benign, borderline and malignant ovarian neoplasm through immunohistochemistry . [METHODS] 1. To culture the ovarian cancer HO8910 cell line with 17-βE2 at different concentration(1×10-10,1×10-9,1×10-8,1×10-7 mol/L) for 72 hours ,then measure the expression of KLK6 mRNA and protein by real-time fluorensence quantitive PCR and flow cytometry respectively and detect the cell proliferation and cell growth cycle by MTT and flow cytometry.2.To examine the expression of hK6 during the 19 cases of benign , 11 cases of borderline and 45 cases of malignant ovarian neoplasms by immunohistochemistry and statistically analyze whether the expression of hK6 correlate with the clinicopathologic variables and prognosis in patients of ovarian cancer.[RESULTS]1. The expression of KLK6 mRNA(3.83±0.41,4.14±0.49,6.26±0.38,7.28±1.82) and protein(10.62±0.35,10.89±0.12,11.88±0.28, 12.07±0.15) in the test group HO8910 cells'(1×10-10,1×10-9,1×10-8,1×10-7mol/L) was obviously higher than the ethanol control group(P<0.01 ).And MTT test shows the cell absorption value (0.7713±0.0151,0.8487±0.0224,0.8577±0.0163,0.8953±0.0310)in the test group HO8910 cells was increased significantly,compared to the ethanol control group(0.4593±0.0638)(p<0.01);while the cell percentage in G0/G1 phase of cell cycle (67.72%,66.98%,66.31%,65.19%) was decreased and the percentagein S phase(17.70%,18.27%,18.55%,19.11%) and G2/M phase (14.58%,14.75%,15.14%,15.70%) increased.2. The expression of hK6 in ovarian cancer tissues (60.0%) was significantly higher than it in the benign(15.8%) and borderline(27.3%) ovarian neoplasm tissues (p<0.01);the expression of hK6 in higher-grade ovarian cancer tissues (68.4%) was higher than it in low-grade(14.3%)(p<0.05);the expression of hK6 in late -stage (stage III) (76.7%) was obviously higher than it in early-stage(stage I or II) (26.7%)(p<0.01); the expression of hK6 was significantly higher in node metastasis (77.8%)than no-metastasis(33.3%)(p<0.01);the expression of hK6 in the cancer tissues that the patients died or their pathogenetic condition recurred or their tumor metastasis during 3 years after their surgery was higher (75.0%) than it in the cancer tissues that the pathogenetic condition of the patients was stable( 42.9%)(p<0.05).CONCLUSION: 1. The expression of KLK6 mRNA and protein was up-regulated in HO8910 cell under the estrogen stimulation. Meanwhile the cell proliferation was enhanced.KLK6 maybe act as a tumor enhancing factor during the development of ovarian cancer.2.The expression of hK6 in ovarian cancer tissues was higher than it in the benign and borderline ovarian neoplasm tissues.;the expression of hK6 was higher in the ovarian cancer tissues with late -stage, higher-grade ,node metastasis and that the prognosis of the patients poor. And hK6 was maybe a new ovarian tumor markers that can predict the prognosis of the patients.
Keywords/Search Tags:Ovarian neoplasms, Immunohistochemistry, Tumor marker, Kallikrein 6, Estrogen
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