OBJECTIVETo investigate the effect of in utero exposure to di-n-butyl phthalate (DBP) on the protein expression in the penile tissue of hypospadiac rats, isolate and identify differentially expressed proteins, and determine the role of the differential expression of Annexin A3 in the development of hypospadia in the rat offspring after maternal exposure to DBP.

METHODSTwenty pregnant SD rats were randomly assigned to an experimental group, intragastrically administered DBP at 800 mg/kg, and a control group, given soybean oil at 5 ml/kg, both for 5 days. Three days after birth, the penises of the newborn rats were removed, and the total protein extracted for 2D-electrophoretic separation and image analysis. Differentially expressed protein spots were screened and identified by mass spectrometry, and the changes in the expression of Annexin A3 detected by Western blotting and immunohistochemistry.

RESULTSThirty-one differentially expressed protein spots were screened, of which 17 were identified by mass spectrometry and the SwissProt database, including pyruvate kinase M2, alpha-enolase, and Annexin A3. Western blot showed that Annexin A3 was mainly located in the urethral epithelia and had a lower expression in the hypospadiac rats (1.851 +/- 0.014, n = 10) than in the controls (2.603 +/- 0.012, n = 10) (P < 0.05).

CONCLUSIONA pedigree of differentially expressed proteins in the penises of DBP-induced hypospadia and normal rats was established by the proteomic method. The differential expression of Annexin A3 may play an important role in the development of hypospadia.

Animals ; Animals, Newborn ; Annexin A3 ; metabolism ; Dibutyl Phthalate ; adverse effects ; Epispadias ; Female ; Hypospadias ; metabolism ; Male ; Maternal Exposure ; Penis ; metabolism ; Pregnancy ; Proteome ; analysis ; Proteomics ; Rats ; Rats, Sprague-Dawley

Annexin A3 ; genetics ; metabolism ; Cells, Cultured ; Guanine Nucleotide Dissociation Inhibitors ; genetics ; metabolism ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lactoylglutathione Lyase ; genetics ; metabolism ; RNA, Messenger ; genetics ; Trichloroethylene ; toxicity ; rho-Specific Guanine Nucleotide Dissociation Inhibitors

OBJECTIVETo explore the potential molecular targets for diagnosis and treatment of gallbladder cancer by analyzing and comparing the proteomes expressed in human gallbladder cancer and benign gallbladder tissues.

METHODSThe proteins expressed were analyzed using two-dimensional gel electrophoresis. The differentially expressed proteins in tumors were also analyzed by mass spectrometry (MS). AnnexinA3 expression was examined by streptavidin peroxidase immunohistochemical technique on paraffin-embedded tissue sections from 50 patients of gallbladder cancer and 38 cases of chronic eholecystitis.

RESULTSProtein extracts of individual sample in each type of tissues were separated on two-dimensional gels. There were forty six differentially expressed proteins in the tissue samples of gallbladder cancer. Seventeen proteins were successfully identified by MS, in which nine proteins were overexpressed in tumors and the other eight proteins were underexpressed. The positive expression rates of annexinA3 in gallbladder cancer was significantly higher than that in chronic cholecystitis, and the difference was statistically significant (74.0% vs 21.1%, P < 0.01). In the gallbladder cancer, no correlation was obtained between annexinA3 and age, gender or histologicl type (P > 0.05), but overexpression of annexinA3 correlated significantly with those cases with a lower histological grading (40.0% vs 82.5%, P < 0.05); lymph node or distant metastasis (40.9% vs 100%, P < 0.05); or a shorter survival time after operation (50.0% vs 93.8%, P < 0.05).

CONCLUSIONSSignificant discrepancies in protein expression exist among gallbladder cancer and benign gallbladder tissues. AnnexinA3 plays an important role in the initiation and progression of human gallbladder cancer.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adult ; Aged ; Annexin A3 ; metabolism ; Carcinoma, Adenosquamous ; metabolism ; pathology ; surgery ; Carcinoma, Squamous Cell ; metabolism ; pathology ; surgery ; Cholecystitis ; metabolism ; Electrophoresis, Gel, Two-Dimensional ; Female ; Gallbladder Neoplasms ; metabolism ; pathology ; surgery ; Gene Expression Profiling ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Metastasis ; Proteome ; metabolism ; Proteomics ; Survival Rate