Erratum

No abstract available.

Time-course Transcriptional Profiling of Human Amniotic Fluid-derived Stem Cells Using Microarray / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To maintain the homeostasis of stem cells and prevent their ability to initiate tumorigenesis, it is important to identify and modify factors that prevent or accelerate stem cell senescence. We used microarrays to attempt to identify such factors in human amniotic fluid (HAF)-derived stem cells. MATERIALS AND METHODS: To identify gene expression changes over a time course, we compared gene expression profiles of HAF-derived stem cells in different passages (1st, 2nd, 4th, 6th, 8th, and 10th) using a Sentrix Human illumina microarray. RESULTS: Of the 25,804 genes in the microarray chip, 1,970 showed an over 2-fold change relative to the control (the 1st passage)-either upregulated or downregulated. Quantitative real-time PCR validated the microarray data for selected genes: markedly increased genes were CXCL12, cadherin 6 (CDH6), and folate receptor 3 (FOLR3). Downregulated genes included cyclin D2, keratin 8, insulin-like growth factor 2 (IGF2), natriuretic peptide precursor B (NPPB) and cellular retinoic acid binding protein 2 (CRABP2). The expression pattern of the selected genes was consistent with the microarray data except for CXCL12 and IGF2. Interestingly, the expression of NPPB was dramatically downregulated along the time course; it was almost completely shut-down by the 10th passage. In contrast, FOLR3 mRNA expression was dramatically increased. CONCLUSION: Taken together, although a function for NPPB and FOLR3 in stem cell senescence has not been reported, our results strongly suggest that NPPB and/or FOLR3 play a significant role in the regulation of stem cell senescence.

Establishment of Leukemia Mouse Model Using Mouse-Derived A20 Leukemic Cells, and Detection of Tumor Cells in Bone Marrow / 한국실험동물학회지

Objectives of this study were to establish a leukemia mouse model in the Balb/c mouse based upon the A20 cell line (murine B-lymphoma/leukemia cell line, H-2d). Here we demonstrate for the first time that A20 cells were infiltrated into tissue and bone marrow, thereby evaluate the feasibility of using A20 leukemic cells as a leukemia model. In the study, changes of behavior, survival rate and histological changes of major organs after intravenous injection of A20 cells (1x105, 1x106 or 1x107) into Balb/c mice were observed. After inoculation of 1x106 cells, animals survived up to 38.3 days, although there were no significant correlation between the number of injected cells and life-span. At 21 and 28 days post-injection, both hematoxylin-eosin and CD45R immunohistochemical stains showed diffuse large B-cell lymphoma in the liver. FACS analysis was performed after injection of fluorescent nanomaterial (MNPs@SiO2 RITC)-labeled A20 cells. The labeled A20 cells were detected in bone marrow from 6 hours post-inoculation, indicative of the cellular infiltration. This is the first study that demonstrated the invasion of A20 cells into the bone marrow of Balb/c model using A20 cells. With the occurrence of systemic lesions following metastasis of the cells into lymph nodes and neighboring tissues via bone marrow infiltration, it is suggested that the A20 cell-inoculated Balb/c miouse could be an animal model of acute lymphocytic leukemia.

Vaccination with a Human Papillomavirus (HPV)-16/18 AS04-Adjuvanted Cervical Cancer Vaccine in Korean Girls Aged 10-14 Years

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Comparison of cell growth suppression in SiHa cervical carcinoma cell line by human papillomavirus type 16 E6/E7 siRNAs / 대한산부인과학회지

OBJECTIVE: Human cervical cancer is caused by the high-risk types of human papillomavirus (HPV) such as HPV16, which possess the E6 and E7 oncogenes, whose expressions are a prerequisite for cancer development. We performed this study to compare the efficacy of antitumor activity by HPV siRNA which silences only E6 or both E6/E7. METHODS: We transfected siRNA 377 (HPV16 E6 siRNA), siRNA 3 (HPV16 E6 siRNA), and siRNA 198 (HPV16 E7 siRNA) into SiHa cell line (siRNA 377 silences only E6, and siRNA 3 and siRNA 198 silence both E6 and E7). We experimented cell counts and morphologic changes 24 and 48 hours after transfection and expressions of HPV16 E6/E7 mRNA by RT-PCR. RESULTS: siRNA 377, siRNA 3, and siRNA 198 suppressed the cell growth. siRNA 3 and siRNA 198 were more potent than siRNA 377 in cell growth suppression. siRNA 377 knocked down the expression of E6 mRNA, and both siRNA 3 and siRNA 198 knocked down the expression of E6/E7 mRNA. CONCLUSION: Our results suggest that simultaneous suppression of E6 and E7 was more potent than E6-specific suppression in cancer cell growth.

Comparative Evaluation of ELISA and Luminex Panel Reactive Antibody Assays for HLA Alloantibody Screening / 대한진단검사의학회지

BACKGROUND: For the detection of HLA antibodies, solid-phase tests using purified HLA antigens are increasingly used. In this study, we analyzed the panel reactive antibody (PRA) test results using ELISA and Luminex methods, and the results were compared with those of crossmatch test. METHODS: A total of 111 sera including 90 sera from kidney transplanted patients were tested. ELISA-PRA was performed using Lambda Antigen Tray Class I and II Mixed kits (One Lambda Inc., USA) and additional test was performed to identify HLA specificities. Luminex-PRA tests were performed using LABScreen Mixed kits (One Lambda Inc., USA) and LIFECODES LifeScreen Deluxe kits (Tepnel Co., USA). RESULTS: The positive rates of PRA were higher in Tepnel (P=0.006) and One Lambda Luminex (P<0.001) methods than ELISA, without significant difference between two Luminex methods (P=0.087). The overall concordance rate among the three PRA tests was 62.2% (69/111). The positive and negative predictive values of PRA tests for the flow cytometric crossmatch were 33.3-45.7% and 85.7-89.5%, respectively. Of the two Luminex methods, One Lambda showed higher positive rate than Tepnel for the detection of class I antibodies. The sensitivity of pretransplant PRA for the detection of posttransplant acute rejection episodes was higher in Luminex (P=0.007 for Tepnel, P=0.003 for One lambda) than ELISA method. CONCLUSIONS: Different methods used to detect HLA antibodies showed discrepant results. As the Luminex method was more sensitive than ELISA for the detection of HLA antibodies, it can be used as a routine test in the transplantation laboratory.

Vascular shutdown effects by tetraarsenic oxide in TC-1 cells implanted C57BL/6 mice / 대한산부인과학회지

OBJECTIVE: Arsenic trioxide (As2O3) is known to have potent anti-vascular activity and significantly suppress solid tumor growth. The present study was conducted to investigate the vascular shutdown effects of a novel arsenic compound, tetraasrsenic oxide (As4O6), in comparison with As2O3 using cervical cancer animal model. METHODS: Mice tumor challenge model was used C57BL/6 mice transplanted with TC-1 cells. After the growth of tumors was reached up 200~250 mm3, mice were divided into 3 groups randomly for control and treatment of either As2O3 or As4O6. As2O3 and As4O6 was treated by i.p. injection. The tumor size was caliperated in twice for weeks and anti-vascular effect were assessed by Evans blue extraction assay and Hoechst 33342 staining. In tumor tissue, histopathological feaure was obserevd by hematoxylin and eosin (H&E) staining. RESULTS: In mice treated with either As2O3 and As4O6 (i.p.), both of As2O3 and As4O6 was significantly suppressed the tumor growth compared with control group. Moreover, effect of As4O6 is more pronounced. These tumor growth inhibition is led to the massive necrosis and vacular shutdown in tumor tissue. CONCLUSION: This study suggests that As4O6 may have potential anticancer activity via vascular shutdown in C57BL/6 mice transplanted with TC-1 cells.

Apigenin-induced apoptosis in cervical cancer cell lines / 대한산부인과학회지

OBJECTIVE: Apigenin is a widely distributed plant flavonoid and was proposed as a potent antitumor agent. In this study, we investigated the anticancer effects of apigenin on human cervical cancer cell lines. For this, the effects of apigenin on growth inhibition and apoptosis were examined and also mRNA expression of E6 and E7, the main causes of development of cervical cancer, was also evaluated. METHODS: To observe the anti-proliferative effects, cervical cancer cell lines, 5x103 cells/well (96 well plate) of Caski, HeLa and C33A were plated and 24 h later treated with apigenin for three days and then MTT assay was performed. For apoptosis analysis, Annexin V-FITC staining was performed. To examine the effect on anchorage-independent growth by apigenin, soft agar assay was performed. The mRNA expression of HPV E6/E7 was examined by quantitative RT-PCR. RESULTS: Apigenin inhibited the growth of all three kind of cervical cancer cell lines (CaSki, HeLa, and C33A) and induced apoptosis in these cell lines. Also, anchorage-independent growth of Caski cells in soft agar was inhibited approximately 3 folds by apigenin treatment. Unexpectedly, mRNA expression level of both E6 and E7 in HeLa cells was not significantly affected by apigenin. CONCLUSION: These studies showed that apigenin inhibits cervical cancer cell growth through the induction of apoptosis. However, mRNA expression of HPV E6/E7 genes was not affected by the treatment of apigenin, indicating that the anti-cancer effect of apigenin in cervical cancer might be mediated via other pathway. Taken together, these results suggest that apigenin may provide a new therapeutic approach for cervical cancer.

Kaempferol induced the apoptosis via cell cycle arrest in human breast cancer MDA-MB-453 cells

The aim of present study was to investigate the effects of kaempferol on cellular proliferation and cell cycle arrest and explore the mechanism for these effects in human breast carcinoma MDA-MB-453 cells. Cells were treated with kaempferol at various concentrations (ranging from 1 to 200 microM) for 24 and 48 hrs. Kaempferol significantly inhibited cancer cell growth in cells exposed to 50 and 10 microM of kaempferol and incubated for 24 and 48 hrs, respectively. Exposure to kaempferol resulted in cell cycle arrest at the G2/M phase. Of the G2/M-phase related proteins, kaempferol down-regulated CDK1 and cyclin A and B in cells exposed to kaempferol. In addition, small DNA fragments at the sub-G0 phase were increased by up to 23.12 and 31.90% at 10 and 50 microM incubated for 24 and 48 hrs, respectively. The kaempferol-induced apoptosis was associated with the up-regulation of p53. In addition, the phosphorylation of p53 at the Ser-15 residue was observed with kaempferol. Kaempferol inhibits cell proliferation by disrupting the cell cycle, which is strongly associated with the induction of arrest at G2/M phase and may induce apoptosis via p53 phosphorylation in human breast carcinoma MDA-MB-453 cells.

Recent Concepts of Human Papillomavirus Vaccine

Two prophylactic human papillomavirus (HPV) vaccines against types 6, 11, 16 and 18 have shown great promise in clinical trials with recent results demonstrating 100% efficacy against persistent HPV infection and development of cervical intraepithelial neoplasia up to five years of follow-up. Published data from the phase-IIb and III trials thus far indicate that the prophylactic HPV L1 virus-like particle vaccine is safe and well-tolerated. It offers HPV-naive women a very high level of protection against HPV persistent infection and cervical intraepithelial lesions associated with the types included in the vaccine. HPV vaccination should be also offered to girls before onset of sexual activity. But there are still questions about several issues of HPV prophylactic vaccination. Prolonged clinical trials should be performed for demonstration of these remaining questions. Finally, prophylactic vaccines against HPV will certainly reduce the incidence of the risk of developing cervical cancer.

Application of experion(TM) assay system for discovery of ovarian cancer serum biomarkers / 대한산부인과학회지

OBJECTIVE: The discovery of new biomarkers for ovarian cancer is clearly necessary for the detection and monitoring of the disease. Experion(TM) automated electrophoresis system can be employed in the identification of differentially expressed proteins in cancer cells. The objective of this study was to discover potential diagnostic serological biomarkers for ovarian cancer. METHODS: We performed protein expression difference analyses for 14 healthy women and 28 ovarian cancer patients with stage I, III and IV using Experion(TM) system. And then we checked the protein expression as silver staining after loading at 8~16% gradient gel for comparison with Experion(TM) gel image. The candidate biomarkers were purified and determined using MALDI-TOF mass spectrometer. RESULTS: The distinctive polypeptide peaks were detected at 115.40, 15.96, 14.8, 11.66, and 10.69 kDa and these five peaks were identified as ceruloplasmin, hemoglobin beta chain, hemoglobin sigma chain, serum amyloid A4, and amyloid related serum protein SAA, respectively. These proteins were significantly different between the sera of normal healthy women and ovarian cancer patients. CONCLUSIONS: Five proteins were found to be significantly different between the sera of normal healthy women and ovarian cancer patients. In addition, Experion(TM) assay system can provide high performance for analysis of ovarian cancer-related proteins by increasing the throughput while maintaining a high level of accuracy.

Retraction: Comparison of As2O3 and As4O6 in the Detection of SiHa Cervical Cancer Cell Growth Inhibition Pathway / Journal of the Korean Cancer Association, 대한암학회지

No abstract available.

Retraction: Tetraarsenic Oxide-mediated Apoptosis in a Cervical Cancer Cell Line, SiHa / Journal of the Korean Cancer Association, 대한암학회지

No abstract available.

Genomic gain and loss of cervical cancer using BAC Chip / 대한산부인과학회지

OBJECTIVE: Cervical cancer has long been linked to the sexually transmitted human papillomavirus (HPV), and the oncoproteins E6 and E7 disrupt the functions of tumour suppressor genes, resulting in genetic alteration. It was shown that loss of heterozygosity at 6p is a common genetic alteration in cervical cancer. However, the molecular genetics of cancer have only recently been understood, and for the development of cervical cancer additional genetic alterations in host cell genes are required. The present study has identified the differential changes of the cervical cancer-associated genetic alterations by a genome-wide array based comparative genomic hybridization (array-CGH). METHODS: We analyzed 15 cases of cervical cancer from St. Mary's hospital of The paraffin-fixed tissue samples were microdissected under microscope and DNA was extracted by the procedures of proteinase K digestion and chloroform extraction. Array-based CGH and genomic PCR were carried out with statistical analyses such as hierarchical clustering and Gene Ontology. The BAC array used in this study consisted of 1,440 human BACs, the space among the clones were approximately 2.08 megabase (Macrogen, Seoul, Korea). RESULTS: All of 15 cases of cervical cancer showed specific gains and losses. The analysis limit of average gains and losses was 53%. A significant positive correlation was found between 1p36.32, 3p14.2, 3q27.1, 7p21.1, 8q24.3 and 11q13.1 changes through the cervical carcinogenesis. The high-level of gain regions, BAC clones encoded GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA and RPS6KA4 genes. Frequently gained BAC clones encoded genes were PRSS8, FUS, COL18A1, PCOLN3, MAFG and ASPSCR1. The genes encoded by frequently lost BAC clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B and NR3C2. Also, hierarchical clustering of the expression data readily distinguished genomic alterations in cervical cancer. A subset of cellular processes from each gene was clustered by Gene Ontology database. CONCLUSION: Using Array-CGH, genomic alterations related to cervical cancer were identified to determine whether induction of chromosomal imbalances occurs prior to carcinogenesis. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes present in the gained or lost clones.

Cell Cycle Regulatory Protein Expression Profiles by Adenovirus p53 Infection in Human Papilloma Virus-associated Cervical Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The tumor suppressor gene, p53, has been established as an essential component for the suppression of tumor cell growth. In this study, we investigated the time-course anticancer effects of adenoviral p53 (Adp53) infection on human ovarian cancer cells to provide insight into the molecular-level understanding of the growth suppression mechanisms involved in Adp53-mediated apoptosis and cell cycle arrest. MATERIALS AND METHODS: Three human cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of Adp53 infection was studied via cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay. RESULTS: Adp53 exerts a significant role in suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53 differentially regulated the expression of genes and proteins, and the gene expression profiles in the SiHa cells revealed that the p21, p53 and mdm2 expressions were significantly up-regulated at 24 and 48 hr. Western blot shows that the p21 and p53 expressionlevels were significantly increased after Adp53 infection. In addition, in all cell lines, both the CDK4 and PCNA protein expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at the G1 phase was induced only in the SiHa and HeLa cells, suggesting that exogenous infection of Adp53 in cancer cells was significantly different from the other HPV-associated cervical cancer cells. CONCLUSION: Adp53 can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest, as well as through the regulation of the cell cycle-related proteins. The Adp53-mediated apoptosis can be employed as an advanced strategy for developing preferential tumor cell-specific delivery.

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer. MATERIALS AND METHODS: Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3~10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software(TM). The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases. RESULTS: A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins weredown-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. CONCLUSION: 2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC.

Identification of hemoglobin-alpha and -beta subunits as potential serum biomarkers for the diagnosis and prognosis of ovarian cancer.

The development of new biomarkers for ovarian cancer is clearly necessary for the improved detection and monitoring of the disease. Surface enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) can be employed in the identification of differentially expressed proteins in cancer cells. The objective of this study was, then, to identify potential diagnostic serological biomarkers for ovarian cancer. We performed protein expression difference analyses of 45 serum samples using SELDI protein chip array. Forty-five sera obtained from ovarian cancer patients (n=35) and normal healthy females (n=10), were profiled on the surface of SELDI protein chip. The candidate biomarkers were purified by CM-Sepharose, and their N-terminal amino sequence was determined. The amounts of hemoglobin (Hb) in cancer patient's sera versus that of normal sera were measured by ELISA. Nine sera proteins that were found to be significantly differentially expressed (P<0.05) between the sera of ovarian cancer patients and that of normal healthy females were selected using the WCX2 array. The most distinctive polypeptide peaks detected in the ovarian cancer samples were at 15.1 and 15.8 kDa and these two peaks were identified as the hemoglobin-alpha (Hb-alpha) and -beta (Hb-beta) chain, respectively. ELISA indicated that the sensitivity for intact Hb level was 77% in sera obtained from ovarian cancer patients, as compared with normal healthy female sera. In conclusion, two ovarian cancer biomarker proteins were discovered and identified as Hb-alpha and Hb-beta. Hb levels were significantly different in ovarian cancer serum samples and those obtained from normal healthy females, as determined by ELISA. Additional studies are required to further validate Hb-alpha and Hb-beta biomarkers.

Proteomic analyses of cervical cancer tissues by two-dimensional gel electrophoresis and mass spectrometry / 대한산부인과학회지

OBJECTIVE: Comparison of protein expressions by two-dimensional gel electrophoresis (2-DE) in normal cervix and squamous cell carcinoma tissues in Korean women. METHODS: Normal cervix and squamous cell carcinoma tissues were solubilized with 2-DE buffer and the first dimension of PROTEAN IEF CELL, isoelectric focusing (IEF), was performed using pH3-10 linear IPG strips of 17 cm. And then running 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and sliver stain. Scanned image was analyzed using PDQuest 2-D softwareTM. Protein spot spectrum was identified by assisted laser desorption/ionization-time of fighting (MALDI-TOF) and the protein mass spectrum identifications were performed by searching protein databases of Swiss-prot/TrEMBL, Mascot and MS-FIT. RESULTS: We found 9 up-regulation proteins (Alpha enolase, Keratin 19 type I, Keratin 20 type I, Keratin 13 type I, beta-actin, Aflatoxin B1 aldehyde reductase 1, Annexin A2, Squamous cell carcinoma antigen 2, unknown), 7 down-reguation proteins (Annexin 1, Myosin regulatory light chain 2, 14-3-3 protein epsilon, Heat shock 27 kDa protein, Hypothetical protein (DKFZP434C1715), Tumor necrosis factor receptor superfamily member 13B, Smoth muscle protein 22-alpha) and 6 up and down-regulation proteins (Tropomyosin 1, Tropomyosin 2, Tropomyosin 3, Serine (or cysteine) proteinase inhibitor, Phosphatidylinositol transfer protein alpha isoform, Src homology 3 domain-containing protein HIP-55) between normal cervix and squamous cell carcinoma cell tissues. CONCLUSION: 2-DE offers total protein expressions between normal cervix and squamous cell carcinoma cell tissues, and searching of differently expressed protein for the diagnostic markers of squamous cell carcinoma tissue.

A case of ovarian metastasis of the recurrent uterine cervical cancer after adjuvant radiation therapy / 대한산부인과학회지

Cervical carcinoma is currently the second most common gynecologic malignancy worldwide with high incidence in developing countries. However, ovarian metastasis in cervical carcinoma is rare. Especially in squamous cell carcinoma of cervical cancer, ovarian metastasis is even more rare. And adenocarcinoma of cervical cancer with gradual increase in incidence, has low ovarian metastasis of 2.0-3.6% in the early stage, although it has high ovarian metastasis in the advanced stage. We experience one case of ovarian metastasis in recurrent cervical adenocarcinoma of stage IB1, and then we report it together with brief review of literatures.

Adenosine 5'-triphosphate induced NF-kappa B and intracellular calcium mobilization in cervical cancer cells / 대한산부인과학회지

OBJECTIVE: To know the effect of adenosine 5'-triphosphate (ATP) on intracellular calcium level and cell proliferation in cervical cancer cells. METHODS: Study design: Four different human cervical cancer cell lines (Caski, C33A, HeLaS3 and SiHa) were used in this study. The change of intracellular calcium level, cell proliferation and the activity of proliferation- and calcium-related transcription factors by extracellular ATP were examined in these cell lines. RESULTS: Extracellular ATP induced calcium mobilization, cell proliferation and the activation of NF-kappa B in all cell lines used. CONCLUSION: These results suggest that calcium mobilization and NF-kappa B dependent signaling pathway play an important role in the cell proliferation by ATP in cervical cancer.