OBJECTIVETo investigate the suppression effect of exogenous fragile histidine triad (FHIT) gene on biological property of MEC-1 cells.

METHODSIn order to study the FHIT function in MEC-1 cells, wild-type FHIT gene was transferred into mucoepidermoid carcinoma MEC-1 cells. The proliferation and kinetics, cell cycle, clonal forming rate, and apoptosis of MEC-1 cells, before and after FHIT gene transfection in vitro, and tumor loci formed on mice after injection of transferred MEC-1 cells in vivo were observed by immunochemical staining, flow cytometry analysis, and so on.

RESULTSIt can be seen that exogenous FHIT gene transfer could significantly inhibit the proliferation and reduce the kinetics of MEC-1 cells in vitro, prolong DT from (21.03+/-0.41) h to (26.86+/-0.71) h, and also keep less cells in cell cycle phase S, whilst more cells in phase G1, Additionally, the exogenous FHIT was found to be able to remarkably suppress MEC-1 cells of forming tumor loci in nude mice by lessen tumor weight, and promote higher differentiation of MEC-1 cells to be mucous cells.

CONCLUSIONExogenous FHIT gene could suppress the proliferation, tumorigenicity and improve the differentiation of MEC-1 cells, in vitro and in vivo.

Acid Anhydride Hydrolases ; Animals ; Apoptosis ; Carcinoma, Mucoepidermoid ; Cell Cycle ; Cell Line, Tumor ; Histidine ; Humans ; Mice ; Mice, Nude ; Neoplasm Proteins ; Transfection

OBJECTIVETo investigate the expression of fragile histidine triad (FHIT) gene protein, FHIT and the possible relationship between FHIT expression and clinicopathological indices in colorectal carcinoma.

METHODSDetecting FHIT protein expression in 60 cases of formalin-fixed, paraffin-embedded colorectal carcinoma by citrate-microwave-SP immunohistochemical method, and analyzing its relationship to histological grade, Dukes' stage and 5-year survival rate.

RESULTS55% of the carcinomas showed a marked loss or absence of FHIT expression compared with their matched normal mucosa. Carcinomas with reduced expression of FHIT correlated with their histological grade, Dukes' stage (P < 0.05) and 5-year survival rate. The distribution of decreased expression of FHIT was 7/16 in grade I carcinoma, 14/30 in grade II, 12/14 in grade III, respectively. The correlation between decreased expression of FHIT and Dukes' staging was 5/11 in stage A, 12/28 in stage B, and 16/21 in stage C. The difference between stage A, B with no lymph nodes metastases and the stage C with lymph nodes metastases was of significance (P < 0.05). The follow-up data of 39 cases showed that in the 5-year survival group, 13/25 were of the low FHIT expression carcinomas, while in 5-year deceased group 12/14 were of the low FHIT expression carcinomas (P < 0.05).

CONCLUSIONSThe reduced expression of FHIT may be associated with decreasing differentiation, metastasis and 5-year survival rate in colorectal carcinoma. It is suggested that decreased FHIT expression plays an important role in the development and progression of the tumor, and thus may become a new prognostic marker in colorectal carcinoma.

Acid Anhydride Hydrolases ; Colorectal Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Proteins ; biosynthesis ; Neoplasm Staging ; Survival Analysis

Acid Anhydride Hydrolases ; Carcinoma, Hepatocellular ; etiology ; genetics ; Humans ; Liver Neoplasms ; etiology ; genetics ; Mutation ; Neoplasm Proteins ; genetics ; RNA, Messenger ; analysis

OBJECTIVETo detect the expression of fragile histidine triad in endometriosis and investigate the pathogenesis of endometriosis.

METHODSimmunohistochemistry was used to examine the expression of Fhit in the eutopic and ectopic endometria of 58 patients with endometriosis and in the endometria in 15 patients with hysteromyoma.

RESULTSThe intensity of Fhit expression decreased in the order of normal endometrium, eutopic endometrium in endometriosis group, and ectopic endometrium. In patients with endometriosis, Fhit expression in the eutopic and ectopic endometria in proliferative phase showed no significant difference from that in secretory phase (P>0.05). Fhit expression in the ectopic endometrium showed significant difference between different r-AFS stages. MOD of ectopic endometrium in stages I-II was significantly higher than that in stages III-IV (P<0.05), but Fhit expression in the eutopic endometrium showed no significant difference (P>0.05). MOD of ovarian endometriosis showed no difference with that of adenomyosis.

CONCLUSIONSFhit may play an important role in the development of endometriosis.

Acid Anhydride Hydrolases ; metabolism ; Adult ; Endometriosis ; metabolism ; pathology ; Endometrium ; metabolism ; Female ; Humans ; Middle Aged ; Neoplasm Proteins ; metabolism

BACKGROUND/AIMS: The fragile histidine triad (FHIT) gene located at chromosome 3p14.2, is a candidate tumor suppressor gene often involved in various tumors. Homozygous deletions, lack or reduced expression of FHIT protein, and alteration of its transcription were frequently observed in several types of primary human cancers and cell lines. In the present study, we examined the expression profiles of aberrant FHIT transcripts to explore the role of FHIT gene in gastric carcinogenesis. METHODS: In 6 gastric cancer cell lines, nested reverse transcription-polymerase chain reaction (RT-PCR) and cDNA sequence analyses were performed to detect and characterize the aberrant FHIT transcripts. RESULTS: In addition to the wild-type FHIT transcript, small-sized transcripts with various numbers and lengths were observed in all of the cell lines examined. cDNA sequence analysis confirmed that different types of truncated transcripts included exonic deletions, insertions of intron 5 sequences between exons, and combinations of both. Most of these transcripts lacked exon 5 in which translation initiation codon is located. Aberrant transcripts with partial exonic deletions due to activation of cryptic splice sites were also observed in 5 cell lines. Additionally, multi-step splice patterns indicative of additional downstream processing, were observed in several cancer lines. CONCLUSIONS: These results suggest that the aberrant FHIT transcripts in gastric cancer cell lines results from faulty splicing, including exon skipping, selection of cryptic splice site, and additional downstream splice processing.
*Acid Anhydride Hydrolases ; Cell Line, Tumor ; Codon, Initiator/genetics ; DNA, Complementary/genetics ; Genes, Tumor Suppressor ; Humans ; Neoplasm Proteins/*genetics ; *Sequence Analysis, DNA ; Stomach Neoplasms/*genetics ; *Transcription, Genetic

OBJECTIVETo study the expression and significance of fragile histidine triad (FHIT) and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust.

METHODSEvery second generation of immortalized human bronchial epithelial cells (BEAS-2B) and human embryo lung fibroblasts (WI-38) were exposed to 100 µg/ml Yunnan tin mine dust for 72 h, until the ninth generation. The cells were subsequently co-cultured from the 11th generation. Experimental setup: B group, B (W) group, B (W 100) group, B100 group, B100 (W) group, B100 (W100) group. The expressions of FHIT and Ki-67 in epithelial cells were determined by the method of immunocytochemistry at the 16th, 26th and 36th generation. The percentage of Ki-67 positive cells was calculated as proliferation index.

RESULTSThe expression of FHIT was observed in BEAS-2B cells. The expression levels of FHIT among B group, B (W) group and B (W 100) group had not instinctive difference. At the 16th generation, the expression of FHIT in the B100 group was decreased compared with that in the B group and the expression of FHIT between B100 (W) group and B100 (W100) group was lower than that in the B100 group. At the 26th generation, the expression of FHIT was decreased compared with that at the 16th generation in the B100, B100 (W) and B100 (W100) groups. However, At the 36th generation, positive expression were observed again in the B100, B100 (W) and B100 (W100) groups and the expression levels were in incremental order. At the 16th, 26th and 36th generation, the proliferation indexes of B group, B (W) group and B (W 100) group were all < 3%. The proliferation indexes of B100, B100 (W) and B100 (W100) were increased step by step with the generation elongation.

CONCLUSIONSFHIT could be a target at which Yunnan tin mine dust induces transformation of BEAS-2B cells. The proliferation activation of BEAS-2B cells can be improved by Yunnan tin mine dust.

Acid Anhydride Hydrolases ; metabolism ; Cell Line ; Cell Transdifferentiation ; China ; Dust ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Lung ; cytology ; Neoplasm Proteins ; metabolism ; Tin ; toxicity

OBJECTIVETo investigate the aberrant methylation of fragile histidine triad (FHIT) gene and to explore possible relationship between the aberrant methylation of FHIT and clinicopathological features in hepatocellular carcinoma (HCC).

METHODSThe hypermethylation of FHIT was detected by the methylation specific PCR (MSP) method in 45 patients with HCC (tumoral and nontumoral tissue), 14 cases of normal livers and 4 HCC cell lines (SK-Hep-1, Hep-G2, Hep-3B and Huh7). The correlation of FHIT methylation and clinicopathological features was analyzed.

RESULTSThe frequencies of hypermethylation of FHIT in tumoral and nontumoral tissue, normal liver and cell lines were 71.1%, 64.4%, 14.3% and 75.0%, respectively. A significant relation between hypermethylation of FHIT and poor survival was present (P = 0.0430).

CONCLUSIONSHypermethylation of FHIT is a frequent and early event in HCC, it might relate to a poor prognosis for patients with HCC.

Acid Anhydride Hydrolases ; genetics ; Adult ; Carcinoma, Hepatocellular ; genetics ; pathology ; surgery ; DNA Methylation ; Female ; Humans ; Liver Neoplasms ; genetics ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; Prognosis

OBJECTIVETo detect the alteration of fragile histidine triad (FHIT) gene and p16 gene during malignant transformation of immortal human bronchial epithelial cell line (16HBE) induced by crystalline nickel sulfide, and study the molecular mechanism of nickel carcinogenesis.

METHODSMalignant transformed cells and tumorigenic cells were examined for the alteration of FHIT gene and p16 gene by RT-PCR, DNA sequencing and silver staining PCR-SSCP.

RESULTSCompared with those of control 16HBE, neither mutation of exon2 or exon2-3, abnormal expression in p16 gene nor mutation of FHIT exon5, 6, 7 and 8, exon1-4 or exon5-9 were observed in transformed cells and tumorigenic cells. But aberrant transcript or FHIT gene expression loss were observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in FHIT gene, the deletion of exon6, exon7 and exon8 and an insertion of 36 bp sequence replacing exon6-8, was confirmed by sequencing.

CONCLUSIONFHIT gene, not p16 gene, could play a definite role in nickel carcinogenesis. Alterations of FHIT gene induced by crystalline NiS could be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation, and FHIT gene could be one of the important target genes activated by exotic carcinogens.

Acid Anhydride Hydrolases ; Base Sequence ; Cell Transformation, Neoplastic ; chemically induced ; metabolism ; Cells, Cultured ; Gene Expression ; Genes, p16 ; physiology ; Humans ; Molecular Sequence Data ; Neoplasm Proteins ; genetics ; metabolism ; Nickel ; pharmacology

BACKGROUNDIt is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Our study aimed to investigate the differential expression of Ki-67, galectin-3, fragile histidine triad (FHIT) gene, and parafibromin in PC, parathyroid adenoma (PA), parathyroid hyperplasia (PH), and normal parathyroid (NP) tissues; then to assess these expression values for use in differential diagnosis of malignant and benign parathyroid tumors.

METHODSData of 15 cases with PC, 19 PAs, and 8 PHs were retrospectively analyzed for their clinical characteristics. The expression of Ki-67, galectin-3, FHIT, and parafibromin were detected via immunohistochemistry in the above-mentioned specimens and 6 NPs as control.

RESULTSComplete loss of parafibromin expression was seen in 9 of 15 (60%) carcinomas, and all normal parathyroid tissues and parathyroid benign tumors stained positive for parafibromin except for one (4%) adenoma. Galectin-3 staining was positive in 11 of 15 (73%) carcinomas, 5 of 19 (26%) adenomas, 1 of 8 (12%) hyperplasias, and 0 of 6 normal tissues. The Ki-67 proliferative index was high in 4 of 15 (27%) carcinomas, 1 of 19 (5%) adenomas, and none of the hyperplasia or normal tissues. FHIT expression did not differ appreciably among the tumor types. The combination of overexpression of galectin-3 or loss of parafibromin increased sensitivity for PC to 87%, while the specificity of both positive galectin-3 and positive Ki-67 could reach 100%.

CONCLUSIONSThese data suggested that loss of parafibromin and overexpression of galectin-3 and Ki-67 might help to distinguish parathyroid carcinoma from other parathyroid tumors. And the combination of two or three of these markers might produce better sensitivity and/or specificity for the diagnosis of parathyroid carcinoma.

Acid Anhydride Hydrolases ; metabolism ; Galectin 3 ; metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Neoplasm Proteins ; metabolism ; Parathyroid Neoplasms ; metabolism ; Tumor Suppressor Proteins ; metabolism

OBJECTIVETo investigate the expressions of the FHIT and PTEN genes and their significance in prostate cancer.

METHODSThe expressions of FHIT and PTEN were detected in 85 cases of prostate cancer and 30 cases of benign prostatic nodular hyperplasia by immunohistochemistry of PV-6000.

RESULTSThe positive expression rates of FHIT and PTEN were 34.1% and 42.4% in prostate cancer, significantly lower than 96.7% and 90.0% in benign prostatic nodular hyperplasia (P <0.01). Statistically significant differences were found in the positive expression rates of FHIT and PTEN among different Gleason grades, 44.4% and 55.6% in well differentiated, 38.9% and 44.4% in moderately differentiated, and 25.0% and 37.5% in lowly differentiated prostate cancer (P <0.05). But the expression of FHIT.

CONCLUSIONFHIT and PTEN may play a certain role in the was not correlated with that of PTEN in the prostate cancer tissue (P >0.05). development, progression and infiltration of prostate cancer.

Acid Anhydride Hydrolases ; metabolism ; Adenocarcinoma ; metabolism ; pathology ; Aged ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; PTEN Phosphohydrolase ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology