PURPOSE: The aim of the study was to determine steroid sulfatase (STS) expression in endometrial cancer patients and its correlation with disease prognosis. MATERIALS AND METHODS: We conducted a retrospective study in 59 patients who underwent surgery with histologically confirmed endometrial cancer from January 2000 to December 2011 at Hanyang University Hospital. Immuno-histochemical staining of STS was performed using rabbit polyclonal anti-STS antibody. RESULTS: Sixteen of the 59 patients (27.1%) were positive for STS expression. Disease free survival (DFS) was 129.83±8.67 [95% confidence interval (CI): 112.84-146.82] months in the STS positive group (group A) and 111.06±7.17 (95% CI: 97.01-125.10) months in the STS negative group (group B) (p=0.92). Overall survival (OS) was 129.01±9.38 (95% CI: 110.63-147.38) months and 111.16±7.10 (95% CI: 97.24-125.07) months for the groups A and B, respectively (p=0.45). Univariate analysis revealed that FIGO stage and adjuvant therapy are significantly associated with DFS and OS. However, in multivariate analysis, FIGO stage and adjuvant therapy did not show any statistical significance with DFS and OS. STS was also not significantly associated with DFS and OS in univariate and multivariate analysis. CONCLUSION: STS expression was not significantly associated with DFS and OS, despite positive STS expression in 27% of endometrial cancer patients. Therefore, the role of STS as a prognostic factor in patients with endometrial cancer remains unclear and requires further research.
Adult ; Aged ; Biomarkers, Tumor ; Combined Modality Therapy ; Disease-Free Survival ; Endometrial Neoplasms/mortality/*surgery ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Steryl-Sulfatase/*metabolism ; Uterine Neoplasms/mortality/pathology/*surgery

Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and has a pivotal role in regulating the formation of biologically active estrogens. STS may be considered a new promising drug target for treating estrogen-mediated carcinogenesis. However, the molecular mechanism of STS expression is not well-known. To investigate whether tumor necrosis factor (TNF)-alpha is able to regulate gene transcription of STS, we studied the effect of TNF-alpha on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-alpha significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with TNF-alpha resulted in a strong increase in the phosphorylation of Akt on Ser-473 and when cells were treated with phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, or Akt inhibitor (Akt inhibitor IV), induction of STS mRNA expression by TNF-alpha was significantly prevented. Moreover, activation of Akt1 by expressing the constitutively active form of Akt1 increased STS expression whereas dominant-negative Akt suppressed TNF-alpha-mediated STS induction. We also found that TNF-alpha is able to increase STS mRNA expression in other human cancer cells such as LNCaP, MDA-MB-231, and MCF-7 as well as PC-3 cells. Taken together, our results strongly suggest that PI 3-kinase/Akt activation mediates induction of human STS gene expression by TNF-alpha in human cancer cells.
Blotting, Western ; Fluorescent Antibody Technique ; Humans ; Male ; Phosphatidylinositol 3-Kinase/genetics/*metabolism ; Phosphorylation/drug effects ; Prostatic Neoplasms/genetics/*metabolism ; Proto-Oncogene Proteins c-akt/genetics/*metabolism ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Recombinant Proteins/genetics/isolation & purification/metabolism ; Signal Transduction ; Steryl-Sulfatase/genetics/*metabolism ; Tumor Cells, Cultured ; Tumor Necrosis Factor-alpha/*pharmacology

OBJECTIVE: This work was demonstrated the induction of apoptosis in response to adriamycin, we checked the cell cycle of adriamycin-induced apoptosis and to investigate whether differential expression is associated with adriamycin-induced genes in human cervical carcinoma HeLa cells. METHODS: Apoptosis was measured by flow cytometry for cell cycle analysis in Hela cells. Differential expression is associated with adriamycin-induced genes in HeLa cells, it was performed to purifiy the RNA, cDNA probe and hybridization. The various different overexpressed genes were determined by gene array analysis (GDA). Analysis were referenced Incyte Genomics Co. (http://www.ncbi.nlm.nih.gov/). RESULTS: We found that adriamycin was induced apoptosis in a dose- and time-dependent manner, as demonstrated by sub-G0/G1 peaks in DNA content histogram of cell cycle. The cells of G2/M phase by treatment of 0.1 microgram/mL adriamycin had been arrested. G2/M peaks in DNA content was decreased in a dose and time-dependent manner. It had been observed 6 group, 16 genes. The group I contained thioredoxin and cytochrome c oxidase subunit IV gene, group II were p53 and excision repair protein (ERCC-1) gene. Group III was metabolic regulated gene, glucosidase, AMP deaminase isoform L (AMPD2), glutamine synthetase, cholesterol 25-hydroxylase, and steryl-sulfatase precursor. Group IV was cell skeleton constructed gene, heparan sulfate proteoglycan (HSPG2), and microfibrillar-associated protein (MFAP2), group V was oncogene group, v-yes-1 Yamaguchi sarcoma viral oncogene homolog-1 (YES1) and tyrosine kinase ELK1. The other group 6 contained NOD1 protein gene interleukine-1 receptor accessory protein (IL1RAP), pregnancy-specific glycoprotein-11 (PSG11), and pregnancy-specific protein-1a (PSG-1a). CONCLUSION: The present findings indicating that adriamycin was revealed apoptosis in Hela cell. Differential gene expression is related in various metabolism by adriamycin.
AMP Deaminase ; Apoptosis* ; Cell Cycle* ; Cholesterol ; DNA ; DNA Repair ; DNA, Complementary ; Doxorubicin ; Electron Transport Complex IV ; Flow Cytometry ; Gene Expression* ; Genomics ; Glucosidases ; Glutamate-Ammonia Ligase ; HeLa Cells* ; Heparan Sulfate Proteoglycans ; Humans* ; Metabolism ; Oncogenes ; Protein-Tyrosine Kinases ; RNA ; Sarcoma ; Skeleton ; Steryl-Sulfatase ; Thioredoxins

OBJECTIVE: This work was demonstrated the induction of apoptosis in response to adriamycin, we checked the cell cycle of adriamycin-induced apoptosis and to investigate whether differential expression is associated with adriamycin-induced genes in human cervical carcinoma HeLa cells. METHODS: Apoptosis was measured by flow cytometry for cell cycle analysis in Hela cells. Differential expression is associated with adriamycin-induced genes in HeLa cells, it was performed to purifiy the RNA, cDNA probe and hybridization. The various different overexpressed genes were determined by gene array analysis (GDA). Analysis were referenced Incyte Genomics Co. (http://www.ncbi.nlm.nih.gov/). RESULTS: We found that adriamycin was induced apoptosis in a dose- and time-dependent manner, as demonstrated by sub-G0/G1 peaks in DNA content histogram of cell cycle. The cells of G2/M phase by treatment of 0.1 microgram/mL adriamycin had been arrested. G2/M peaks in DNA content was decreased in a dose and time-dependent manner. It had been observed 6 group, 16 genes. The group I contained thioredoxin and cytochrome c oxidase subunit IV gene, group II were p53 and excision repair protein (ERCC-1) gene. Group III was metabolic regulated gene, glucosidase, AMP deaminase isoform L (AMPD2), glutamine synthetase, cholesterol 25-hydroxylase, and steryl-sulfatase precursor. Group IV was cell skeleton constructed gene, heparan sulfate proteoglycan (HSPG2), and microfibrillar-associated protein (MFAP2), group V was oncogene group, v-yes-1 Yamaguchi sarcoma viral oncogene homolog-1 (YES1) and tyrosine kinase ELK1. The other group 6 contained NOD1 protein gene interleukine-1 receptor accessory protein (IL1RAP), pregnancy-specific glycoprotein-11 (PSG11), and pregnancy-specific protein-1a (PSG-1a). CONCLUSION: The present findings indicating that adriamycin was revealed apoptosis in Hela cell. Differential gene expression is related in various metabolism by adriamycin.
AMP Deaminase ; Apoptosis* ; Cell Cycle* ; Cholesterol ; DNA ; DNA Repair ; DNA, Complementary ; Doxorubicin ; Electron Transport Complex IV ; Flow Cytometry ; Gene Expression* ; Genomics ; Glucosidases ; Glutamate-Ammonia Ligase ; HeLa Cells* ; Heparan Sulfate Proteoglycans ; Humans* ; Metabolism ; Oncogenes ; Protein-Tyrosine Kinases ; RNA ; Sarcoma ; Skeleton ; Steryl-Sulfatase ; Thioredoxins