Apoptosis ; Cell Proliferation ; Humans ; Liver Neoplasms ; genetics ; metabolism ; pathology ; Neoplasm Proteins ; genetics ; RNA Interference ; Securin

OBJECTIVE: To investigate the expression of tumor-transforming gene-1 (PTTG1) in systemic sclerosis (SSc) and its role in fibrosis. METHODS: Skin biopsy samples were collected from 21 patients with SSc and 22 patients with healthy skin for detecting the mRNA and protein expressions of PTTG1 using real-time PCR (RT-PCR) and immunohistochemistry, respectively. In cultured primary human dermal fibroblasts, PTTG1 expression was knocked down via RNA interference (siRNA), and the mRNA expression levels of PTTG1 and the fibrosis-related genes RESULTS: Compared with those in normal skin samples, the mRNA and protein expressions of PTTG1 increased significantly in the skin tissue of patients with SSc ( CONCLUSIONS PTTG1 is highly expressed in skin tissues of patients with SSc, and PTTG1 knockdown can reduce the activity of the dermal fibroblasts, suggesting a close correlation of PTTG1 with fibrosis in SSc.
Cells, Cultured ; Fibroblasts ; Fibrosis ; Humans ; Scleroderma, Systemic/pathology* ; Securin ; Skin/pathology*

PURPOSE: The anaphase-promoting complex (APC) is a multiprotein complex with E3 ubiquitin ligase activity and is required for ubiquitination of securin and cyclin-B. Several APC-targeting molecules are reported to be oncogenes. Dysregulation of APC may be associated with tumorigenesis. This study examines the relationship between APC expression and clinicopathological factors and evaluates the possibility of an aberrant APC function in colorectal carcinomas (CRCs). METHODS: To determine whether the loss of APC7 expression is related to tumorigenesis, we used tissue micro-arrays in 114 resected CRCs to scrutinize the expressions of APC7 and Ki-67 immunohistochemistry and to find relations with clinocopathologic parameters. The expression of APC7 was defined as positive for summed scores of staining intensities from 0 to 3+. RESULTS: Forty-four cases (67.7%) of colon cancer and 38 cases (77.6%) of rectal cancer showed immunopositive reactions to APC. The grade of APC expression was not statistically correlated with tumor location, age, T or TNM stage, or differentiation. However, the expression of APC did correlate with the expression of Ki-67 and to the tumor recurrent. Higher APC expression showed the better 5-year overall survival rate in 74% of grades 2, 3 groups (high expression) than 57% of grades 0, 1 groups (lower expression) respectively (P = 0.042). CONCLUSION: Positive APC expression may be a good prognostic factor for patients with CRC, and the loss of APC expression in tumor tissue may be related with the risk for recurrence and a poor survival rate compared to high APC expression. Further study of APC in controlling the cell cycle as aberrant function in CRC is needed.
Adenocarcinoma ; Anaphase-Promoting Complex-Cyclosome ; Carcinogenesis ; Cell Cycle ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans* ; Immunohistochemistry ; Oncogenes ; Rectal Neoplasms ; Recurrence ; Securin ; Survival Rate ; Ubiquitin ; Ubiquitin-Protein Ligases ; Ubiquitination

Objective To study the stemness characteristics of uterine corpus endometrial carcinoma(UCEC)and its potential regulatory mechanism.Methods Transcriptome sequencing data of UCEC was obtained from The Cancer Genome Atlas.Gene expression profile was normalized by edgeR package in R3.5.1.A one-class logistic regression machine learning algorithm was employed to calculated the mRNA stemness index(mRNAsi)of each UCEC sample.Then,the prognostic significance of mRNAsi and candidate genes was evaluated by survminer and survival packages.The high-frequency sub-pathways mining approach(HiFreSP)was used to identify the prognosis-related sub-pathways enriched with differentially expressed genes(DEGs).Subsequently,a gene co-expression network was constructed using WGCNA package,and the key gene modules were analyzed.The clusterProfiler package was adopted to the function annotation of the modules highly correlated with mRNAsi.Finally,the Human Protein Atlas(HPA)was retrieved for immunohistochemical validation.Results The mRNAsi of UCEC samples was significantly higher than that of normal tissues(
Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; Endometrial Neoplasms/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mad2 Proteins ; Multigene Family ; Neoplastic Stem Cells ; Prognosis ; Securin

ObjectiveTo explore the expression of pituitary tumor transforming gene 1 (PTTG1) during the transformation of prostate cancer from androgen-dependent (ADPC) to androgen-independent (AIPC).

METHODSWe established an AIPC cell model LNCaP-AI by culturing the androgen-dependent LNCaP cell line in the hormone-deprived medium for over 3 months. The cell model was verified and the PTTG1 expression in the LNCaP cells was detected by Western blot and RT-PCR during hormone deprivation.

RESULTSThe AIPC cell model LNCaP-AI was successfully established. The PTTG1 expression was gradually increased in the LNCaP cells with the prolonged time of hormone deprivation and the expressions of matrix metalloproteinases MMP-2 and -9 were elevated at the same time.

CONCLUSIONSThe expression of PTTG1 is increased gradually in AIPC, which may be a target of gene therapy for advanced prostate cancer.

Blotting, Western ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasms, Hormone-Dependent ; Prostatic Neoplasms ; enzymology ; genetics ; Securin ; genetics

OBJECTIVETo explore the expression of pituitary tumor transforming gene (PTTG) in human renal clear cell carcinoma (RCCC) and its significance.

METHODSPTTG protein expression was detected by immunohistochemistry in 87 RCCC and 45 paired normal renal tissues.

RESULTSPTTG was expressed differentially between the normal renal and RCCC tissues. Compared with normal tissues, the primary RCCC tissues showed significantly increased expression of PTTG protein (P<0.001). The positive rate of PTTG protein was positively correlated to the tumor size, clinical stage and Fuhrman grade of RCCC (P=0.009, 0.008 and 0.035, respectively).

CONCLUSIONIncreased PTTG protein expression may be involved in the carcinogenesis and progression of RCCC.

Adult ; Aged ; Carcinoma, Renal Cell ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; metabolism ; Securin

The aim of study was to explore the expression of pituitary tumor-transforming gene (pttg) in acute myeloid leukemia (AML) and its relationship with the pathogenesis of AML, simultaneously to investigate the difference of the pttg expression among AML different subtypes. The expressions of pttg mRNA were quantitatively detected by real-time fluorescence quantitative polymerase chain reaction (real-time PCR) in bone marrow from 47 patients with AML and 28 normal controls. The results indicated that the expression of pttg mRNA was significantly higher in AML patients [(1.1323 ± 1.3934) × 10(5)] than that in normal controls [(4.5766 ± 1.1817) × 10(3)] (p < 0.05). The expression of pttg mRNA was higher in M(3) patients than that in other AML subtypes, such as M(1), M(2), M(4), M(5). It is concluded that the overexpression of pttg may be related to the pathogenesis and progression of AML, in which the overexpression of pttg may be more intimately related to the pathogenesis and progression of M(3). This study provides a new idea to research the pathogenesis and targeted gene therapy of AML.
Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; RNA, Messenger ; metabolism ; Securin ; Young Adult

Objective: To investigate the effects of down-regulation of PTTG1 expression on the proliferation, invasiveness and apoptosis of androgen-independent human prostate cancer LNCaP-AI cells and their sensitivity to androgen antagonists. METHODS: Human prostate cancer LNCaP-AI cells were transfected with siRNA targeting the PTTG1 gene using the Lipofectamine 2000 transfection reagent. The proliferation, invasiveness and apoptosis of the cells were detected by MTT, Transwell assay and flow cytometry, respectively. The protein expressions of PTTG1, p-Akt, and p-ERK were determined by Western blot and the mRNA expression of PTTG1 measured by agarose gel electrophoresis. RESULTS: The siRNA expression vector markedly down-regulated the expression of PTTG1, which effectively suppressed the proliferation of the LNCaP-AI cells, with the inhibition rates of (19.47 ± 2.12), (24.01 ± 2.13) and (48.02 ± 2.22)% at 24, 48 and 72 hours, respectively, after transfection, with statistically significant differences among the three groups (P <0.05). The number of the cells passing through the polycarbonate film was remarkably decreased at 24, 48 and 72 hours (74.67 ± 9.85, 56.44 ± 8.66 and 37.33 ± 6.14) as compared with the baseline (111.11 ± 13.47) (P <0.01), while the apoptosis rate of the cells was significantly increased at 24, 48 and 72 hours (18.32 ± 0.94), (19.94 ± 1.30) and (21.73 ± 1.88)% in comparison with the baseline (［2.17 ± 0.49］%)， (P <0.05). PTTG1 siRNA combined with androgen antagonist flumatide exhibited even more significant effects in inhibiting the proliferation and promoting the apoptosis of the LNCaP-AI cells than either used alone, and in a flumatide dose-dependent manner. The inhibition and apoptosis rates of the LNCaP-AI cells treated with 50 nmol/L flumatide were (27.13 ± 3.52) and (3.94 ± 0.48)%, and those treated with siRNA + 50 nmol/L flumatide were (67.51 ± 5.13) and (19.93 ± 1.72)%, respectively, both with statistically significant differences between the two groups (P <0.05). The inhibition and apoptosis rates of the cells treated with 100 nmol/L flumatide were (43.72 ± 3.90) and (5.33 ± 0.66)%, and those treated with siRNA + 100 nmol/L flumatide were (73.19 ± 4.78) and (23.43 ± 1.76)%, respectively, both with statistically significant differences between the two groups (P <0.05). CONCLUSIONS The siRNA expression vector can down-regulate the expression of PTTG1, which can inhibit the proliferation and invasiveness of LNCaP-AI cells, promote their apoptosis, and increase their sensibility to androgen antagonists. Suppressing the expression of PTTG1 may enhance the effect of androgen-deprivation therapy on advanced prostate cancer.
Androgen Antagonists ; pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Humans ; Male ; Neoplasm Invasiveness ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology ; RNA, Small Interfering ; metabolism ; Securin ; genetics ; metabolism ; Time Factors ; Transfection

The study was purposed to explore the expressions of pituitary tumor transforming gene and c-myc gene in patients with multiple myeloma (MM) and its relationship with pathogenesis of MM. Expressions of pituitary tumor transforming gene and c-myc gene mRNA in BMMNC from 33 patients with MM and 10 normal controls were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the expressions of pituitary tumor transforming gene and c-myc gene mRNA were significantly higher in MM patients those that in normal controls (p<0.05). The expression of pituitary tumor transforming gene mRNA was significantly correlated with the expression of c-myc gene (r=0.801, p<0.05). In conclusion, the overexpressions of pituitary tumor transforming gene and c-myc gene may be related to the pathogenesis and progression of MM.
Adolescent ; Adult ; Aged ; Case-Control Studies ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; genetics ; Neoplasm Proteins ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism ; RNA, Messenger ; genetics ; Securin ; Young Adult

To investigate the expression of pituitary tumor-transforming gene (PTTG) and basic fibroblast growth factor (b-FGF) in acute leukemia, as well as the relationship of their expression with prognosis in acute leukemia, expressions of PTTG and b-FGF in acute leukemia (AL) specimens were detected by immunocytochemical technique. The results showed that the expressions of PTTG and b-FGF in AL group were higher than that in the control group significantly (P < 0.01). In AL group, after chemotherapy, the expression of PTTG and b-FGF in de novo patients group was higher than in the complete remission patient group significantly (P < 0.01). The expressions of PTTG and b-FGF showed positive correlation (r = 0.61, P < 0.01). It is concluded that Up-regulation of PTTG and b-FGF expression may be involved in the progression of acute leukemia and correlated closely with therapeutic effect. Associated detection of PTTG and b-FGF may help to judge the malignancy degree and prognosis of acute leukemia.
Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; biosynthesis ; Child ; Female ; Fibroblast Growth Factor 2 ; biosynthesis ; Humans ; Immunohistochemistry ; Leukemia ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Proteins ; biosynthesis ; Prognosis ; Securin