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Results for “Genes, p16”

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At least 19 recordsLinked to original sources

PubMed2003

[Alteration of FHIT gene and p16 gene in malignant transformed cells induced by crystalline nickel sulfide].

OBJECTIVE: To 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. METHODS: Malignant 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. RESULTS: Compared 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. CONCLUSION: FHIT 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↗

PubMed2006

Alterations of FHIT gene and P16 gene in nickel transformed human bronchial epithelial cells.

OBJECTIVE: To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. METHODS: 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. RESULTS: NiS-treated cells exhibited overlapping growth. Compared with that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases (P < 0.01) and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in p16 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. CONCLUSIONS: The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.

Acid Anhydride Hydrolases↗

PubMed1999

[Alterations of FHIT gene and p16 gene in lung cancer and metastatic hilar lymph nodes].

OBJECTIVE: To investigate alterations of fragile histidine triad (FHIT) gene and p16 gene in lung cancer. METHODS: Forty-nine lung cancer specimens and 16 matched metastatic hilar lymph nodes of lung cancer patients were examined for abnormalities of p16 and FHIT genes by using RT-PCR and RT-PCR-SSCP. RESULTS: Thirty-two of 47(68.1%) samples of primary lung cancer and 15 of 16 (93.8%) samples of metastatic hilar lymph nodes exhibited loss of FHIT gene transcripts. In 14 of the 47 samples of primary lung cancer(29.8%), and 9 of 16 samples of metastatic hilar lymph nodes(56.3%), FHIT gene transcripts were deleted in exones 1-4. The deletion rate of p16 gene transcripts in exons 2-3 was 36.7% (18/49) in primary and 56.3% (9/16) in metastatic lymph nodes, respectively. The loss of p16 or FHIT expression did not correlate with sex, smoking, TNM stage, but was more frequently observed in poorly differentiated cancer. No mutation of FHIT and p16 cDNA was found by SSCP. CONCLUSIONS: Loss of FHIT and p16 gene transcript is frequent in lung cancer and may be an early event in lung carcinogenesis. Mutations may not be the major mechanisms of p16 and FHIT gene inactivation. Lung cancer with FHIT and p16 gene alterations have more malignant phenotype and behavior.

Acid Anhydride Hydrolases↗

PubMed2001

[Effect of exogenous p16 gene on biological behaviors of human lung cancer].

OBJECTIVE: To evaluate the biological effects of tumor suppressor gene p16 on human lung cancer cells with p16 gene deletion. METHODS: p16-pcDNA3 was transfected into lung cancer cell line A549 using lipofectin, in which p16 gene was homozygously deleted. Biological behaviors of the transfected cell line were investigated both in vitro and in vivo. The expressions of p16 mRNA and protein were detected by RT-PCR and immunohistochemistry. RESULTS: There was stable expression of p16 in the transfected cell line A549. Exogenous p16 gene significantly slowed down the growth of A549 cells as compared with the control. Flow Cytometry showed that the transfected cells were stagnated in G1 phage of cell cycle accompanying with apoptosis. In addition, clonogenic assay showed that the number of colony in soft agar was decreased in transfected cells as well. In vivo, a suppressed tumorigenicity and significantly decreased growth rate were shown in nude mice injected with A549 cells transfected with p16-pcDNA3, as compared with those in mice injected with either original A549 or A549 transfected with pcDNA3. CONCLUSION: Exogenous p16 gene can express stably in human lung cancer A549 cell line; exogenous p16 gene transfection induces apoptosis in lung cancer cells with p16 deletion and inhibits growth of the tumor in nude mice.

Animals↗

PubMed1999

[Apoptosis of human melanoma cell line WM-983A by p16 gene transduction].

OBJECTIVE: To further understand the mechanism of action of the tumor-suppressor gene p16. METHODS: An adenoviral expression vector with full length cDNA of p16 gene insert was constructed (Ad-p16) and transfected into WM-983A cells, the p16 gene of which was point mutated at codon 126. The effect of exogenous p16 gene on the growth of WM-983A cells was examined in vitro and in vivo. RESULTS: Expression of p16 gene in WM-983A cells was confirmed by Western blot. The in vitro growth of the Ad-p16 transfected WM-983A cells was significantly inhibited (inhibition rate: 78%) as compared to mock (Ad-LacZ) transfected WM-983A cells. Colony-forming activity in vitro of the Ad-p16 transfected WM-983A cells was completely inhibited. Morphologically, the Ad-p16 transfected cells appeared apoptotic which was confirmed by the appearance of pre-G1 on flow cytometry and DNA fragmentation. The growth of WM-983A xenografts in nude mice was retarded by intra-tumoral injection of Ad-p16. CONCLUSION: p16 gene participates in the induction of cell apoptosis. It is promising to use it for gene therapy of cancer, especially when combined with other apopptosis-inducing agents.

Animals↗

PubMed2004

[Significance of methylation and abnormal expression of p16 gene in endometrial carcinoma].

The tumor suppressor gene p16, located on chromosome 9p21, encodes the cell cycle regulatory protein, p16. Inactivation of the p16 gene could lead to uncontrolled cell growth. It was examined that methylation of the p16 gene 5'CpG island of the tumor suppressor gene may be an important mechanism for transcriptional inactivation. In order to determine the role of methylation status of the 5'CpG island and abnormal expression of incarcinogenesis of endometrial carcinoma (EC), Methylation-Specific PCR (MSP) was used to determine the methylation status of p16 gene 5'CpG islands of 62 cases of EC. Loss or decrease of p16 expression was analyzed by immunohistochemistry (IHC) and homozygous deletion of exon1 (E1) and exon2 (E2) was determined by complex PCR. Ten specimens of normal tissues and adjacent tissues of tumor displayed no methylation and showed normal expression of p16. In E1 and E2 of the 62 EC, we found that 24.2% (15/62) were methylated, 54.8% (33/62) lost or reduced p16 expression, 16.1% (10/62) and 30.6% (19/62) had deletions of E1 and E2 respectively. There were 9.68% (6/62) and 46.6% (29/62) deletions of both or either of E1 and E2 respectively. Inactivation of p16 gene is a frequent event and positively correlated with pathological grades and clinical stages in EC. p16 gene methylation was an important event in the development of EC. MSP is an accurate and relatively simple method for evaluating the methylation status of a related gene.

DNA Methylation↗

PubMed2001

The correlation between alteration of p16 gene and clinical status in oral squamous cell carcinoma.

The purpose of the study was to evaluate the presence of alteration of the tumor suppressor gene p16 and to correlate these changes with the clinical status of the patients in oral squamous cell carcinoma. Forty-eight oral squamous cell carcinomas were included in the analyses. Deletion analysis was performed by the polymerase chain reaction (PCR). Mutation analysis was restricted to exon 1 and exon 2 of the p16 gene, previously shown to have a high incidence of mutations. The sequences containing exon 1 and exon 2 were amplified by PCR and screened with a single-strand conformation polymorphism (SSCP) technique. Samples showing band shifts in SSCP were sequenced by PCR direct sequencing. Western blots were used to detect the protein expression of the p16 gene, and the results were evaluated with regard to their biological relevance in correlation with clinicopathological factors. Seven (14.6%) deletions were found; 5 (10.4%) mutations were discovered and located in different codons; 26 (54%) specimens had no p16 protein expression; in 11 specimens with p16 deletion or mutation, p16 protein could not be detected. One mutation was non-sense. The p16 gene alterations showed no relationship with location and clinical stage of cancer; however, a close relationship between p16 alterations and cancer metastasis to neck lymph node was found. The alteration rate gradually elevated from well to poorly differentiated grades. We perceive two results. First, the alterations of the p16 gene are common in oral squamous cell carcinoma. Second, the alterations of the p16 gene may attribute to the metastatic behavior or histological grade of cancer cells.

Adult↗

PubMed1997

Alterations of the p16 gene in head and neck cancer: frequency and association with p53, PRAD-1 and HPV.

Alterations, especially homozygous deletions, of the putative tumor suppressor gene, p16 (p16INK4A, MTS1, CDKN2) have been found in tumor cell lines from a variety of neoplasms. Recent studies have reported frequent p16 gene deletions in cell lines from squamous cell carcinomas of the head and neck (SCCHN), although the prevalence of alterations was variable in primary tumors. This study determined the prevalence of point mutations and deletions of the p16 gene in 33 SCCHN. In addition, the association of p16 gene alterations and abnormalities of p53, PRAD-1 (cyclin D1), and the presence of human papillomavirus (HPV) was examined. We found an overall prevalence of p16 alterations of 36% (nine deletions, three single base substitutions, including one polymorphism). Seven tumors (of 29, 24%) had an alteration of p16 and p53; five (of 33, 15%) had alterations of p16 and PRAD-1; three (of 29, 10%) had alterations of all three genes. In addition, of the five tumors with human papillomavirus detected, only one also had a p16 gene alteration. The results indicate a potentially important role for the p16 gene in head and neck tumorigenesis. In addition, the presence of tumors with multiple somatic gene alterations suggest a possible interaction in the dysregulation of the cell cycle.

Adult↗

PubMed2005

[Hypermethylation of CpG island of p16 gene and arsenic trioxide induced p16 gene demethylation in multiple myeloma].

OBJECTIVE: To investigate the role of hypermethylation of p16 gene in the pathogenesis of multiple myeloma (MM) and the effect of arsenic trioxide (As2O3) induced p16 gene demethylation. METHODS: Methylation status of p16 gene in MM and U266 cell line exposed to As2O3 were detected the nested-methylation specific PCR. The expression of p16 gene mRNA was determined with RT-PCR. The induced growth inhibition of U266 cell by growth curve and MTT and the DNA content of U266 cell were analyzed with flow cytometry after exposure to As2O3. RESULTS: Hypermethylation of CpG island of p16 gene was observed in 54.8% of the MM patients in our group. p16 gene fail to express in U266 cell line after methylation. As compared with beta-actin, the expression of p16 gene mRNA in U266 cell was increased to 0.22 +/- 0.10, 0.59 +/- 0.11, 0.68 +/- 0.09 after exposure to 0.5 micromol/L, 1.0 micromol/L and 2.0 micromol/L As2O3 for 72 h. CONCLUSIONS: These results indicate that methylation of p16 gene is essential important in the pathogenesis of MM and may provide a new diagnostic technique and drug target for the treatment of MM. As2O3 may activate the expression of p16 gene by demethylation.

Aged↗

PubMed2005

Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma.

BACKGROUND: Stepwise progression of peripheral-type lung adenocarcinoma was characterized morphologically and was related to prognosis. Expression of the tumor suppressor gene p16 in pulmonary adenocarcinoma decreased, mainly as a result of aberrant methylation of the CpG islands of the promoter region. METHODS: Aberrant methylation status of the p16 promoter region, the expression of its product, and loss of heterozygosity (LOH) on 9p21 were examined in surgically resected lung specimens from 57 patients (28 males and 29 females) with peripheral-type lung adenocarcinoma measuring </= 2 cm in diameter. RESULTS: Aberrant methylation of the p16 promoter region, negative p16 protein expression, and LOH of the 9p21 region were detected in 40.4%, 50.9%, and 40.4% of tumor samples, respectively. The alterations of the p16 gene were associated with poor prognosis, and in particular the prognosis of patients with aberrant p16 methylation was significantly worse than that of patients without aberrant methylation. These alterations also were associated with morphologic classification into bronchioloalveolar carcinoma (BAC) and non-BAC adenocarcinoma. Both aberrant methylation and LOH of 9p21 were associated with negative protein expression, but the former was correlated more closely with loss of function than was the latter. Cases with both alterations were completely negative for expression of the p16 gene product. CONCLUSIONS: Aberrant methylation of the promoter region of the p16 gene and loss of expression of its product were in accord with the multistep progression of peripheral-type lung adenocarcinoma, and these alterations were associated closely with poor prognosis of the disease.

Adenocarcinoma↗

PubMed2006

Clinicopathological roles of alterations of tumor suppressor gene p16 in papillary thyroid carcinoma.

BACKGROUND: Alterations of the p16 gene are common in human cancers, but their roles in thyroid cancers have not been clearly defined. The aim of the present study was to investigate the clinicopathological roles of the p16 gene in papillary thyroid carcinoma (PTC). METHODS: p16 gene alterations were investigated in 44 patients with PTC (9 men, 35 women) by immunohistochemistry, reverse transcriptase-polymerase chain reaction and methylation-specific polymerase chain reaction. The findings were correlated with their clinicopathological features. RESULTS: p16 protein expression, mRNA alterations, and promoter methylation were detected in 89% (n = 39), 77% (n = 33), and 41% (n = 18) of patients with PTC, respectively. There was no marked relationship between p16 protein expression, mRNA alteration, and promoter methylation. In follicular variant of PTC (FVPTC), there was a frequent lack of p16 protein expression and promoter methylation. PTCs showing p16 promoter methylation were often associated with a high AMES (age, metastasis to distant sites, extrathyroidal invasion, size) risk group and advanced pTNM (tumor-lymph node-metastasis) stages. CONCLUSIONS: p16 gene alterations are common and correlate with histological features and biological aggressiveness in PTC, suggesting that they might play an important role in its pathogenesis.

Adenocarcinoma, Follicular↗

PubMed2000

Adenovirus p16 gene therapy for prostate cancer.

Surgery, radiation, or hormone deprivation alone does not adequately affect local control of clinical or pathologic stage T3 prostate cancer. Lack of local cancer control ultimately leads to a higher incidence of morbidity, distant metastasis, and decreased survival, with patients having disease-specific mortality exceeding 75%. Other novel therapies against this devastating and common disease are needed for the achievement of long-term local cancer control. For this purpose, therapeutic interventions should target prostate-cancer cells at the molecular and cellular level in ways not possible by current modalities of cancer treatment. Any strategy that can modify the biologic behavior of these cells may potentially have the most significant clinical impact. As prostate cancer represents an accumulation of genetic mutations that causes a prostate cell to lose the ability to control its growth, one new approach against prostate cancer may be gene therapy. Identification of key missing or mutated tumor-suppressor genes that, when replaced, may inhibit or destroy prostate-cancer cells may have the best chance of clinical success. One such gene appears to be tumor-suppressor gene p16 (also known as MTS1, INK4A, and CDKN2). Tumor-suppressor gene p16 is an important negative cell-cycle regulator whose functional loss may significantly contribute to malignant transformation and progression. Alterations in the p16 gene and its protein expression often occur in prostate cancer. An adenoviral vector containing wild-type p16 (Adp16) had a high transduction efficiency in prostate-cancer cells both in vitro and in vivo. Moreover, prostate tumors injected with Adp16 expressed p16 and the adenoviral vector expressed the transgene for up to 14 days. Wild-type p16 inhibited prostate-cancer proliferation in vitro and markedly suppressed tumors in vivo. Pathologic evaluation of the Adp16-treated tumors showed dose-dependent necrosis and fibrosis. Although the mechanism of p16 inhibition in cancer remains to be elucidated, senescence and apoptosis may both be important; however, the data suggest that p16-induced growth inhibition can function independently of the retinoblastoma gene product.

Adenoviridae↗

PubMed2000

Changes of the p16 gene but not the p53 gene in human chondrosarcoma tissues.

The role of two important tumour suppressor genes, p16 and p53, was evaluated in cartilaginous tumour tissues. Genomic DNA from 22 chondrosarcomas, 5 benign chondroid tumours, 1 sample of reactive proliferative cartilage and 2 samples of normal cartilage were analysed using polymerase chain reaction, single strand conformational polymorphism, DNA sequencing and methylation-specific polymerase chain reaction. The p16 gene was found to be partly methylated in 5 high-grade chondrosarcomas and homozygously deleted in 1 chondrosarcoma. Moreover, a polymorphism was detected in 3 malignant tumours, but not in benign tumours or normal cartilage. Analysis of the p53 gene revealed an unchanged structure in all samples. These findings show a role for p16, but not p53, in chondrosarcoma.

Adolescent↗

PubMed2001

[Effects of inorganic arsenicals on the methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells].

OBJECTIVE: To study the effects of inorganic arsenicals on the methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells. METHODS: The methylation of p16 gene CpG islands and the expression of p16 gene in BEP2D cells were measured by methylation-specific PCR (MSP) and RT-PCR methods. RESULTS: (1) The exposure of the BEP2D cells to sodium arsenite (0.016 approximately 2 micromol/L) or high-density sodium arsenate (80 approximately 160 micromol/L), but not low-density sodium arsenate (20 approximately 40 micromol/L), produced significant hypermethylation of p16 gene CpG islands in BEP2D cells. (2) The expressions of p16 gene in the groups of sodium arsenite and sodium arsenate at the test were lower than that of the control group, especially in the groups of sodium arsenite. CONCLUSIONS: Inorganic arsenicals alter the methylation patterns and the expression of p16 gene in BEP2D cells, which suggests that the hypermethylation of p16 gene CpG islands may be one of the mechanisms of carcinogenesis of inorganic arsenicals.

Arsenic↗

PubMed2006

p16 gene alterations in locally advanced squamous cell carcinoma of the head and neck.

We previously documented the presence of mutations/deletions in the tumor suppressor gene p16 in squamous cell carcinoma of the head and neck (SCCHN). However, the association of these p16 alterations with clinical outcome is unknown. In this study, RNA was isolated from 19 frozen SCCHN from 19 patients who were previously enrolled in the OSU intensification regimen 2. Quantitative real-time RT-PCR and direct sequencing analysis was then performed on the specimens to detect p16 gene alterations. Clinical outcome for each patient was updated and correlated with the p16 alterations found. Five tumor specimens were found to have no or very low expression of p16 when compared with normal tissue. The remaining 14 tumor samples demonstrated overexpression of p16 relative to the level of expression in normal tissue. Sequence analysis of the p16 RT-PCR product from these specimens allowed identification of mutational changes in the coding sequence of p16 in four of the SCCHN specimens. Subsequent analysis of clinical outcome associated with locoregional/distant failure demonstrated no correlation with either altered expression of p16 or mutational status of p16. Results from this study indicate that p16 alterations are frequently found in this cohort of SCCHN. However, p16 alterations alone do not appear to be associated with clinical outcome.

Adult↗

PubMed1998

p16 gene overexpression in mouse bladder carcinomas.

Deletion of 9p21 has frequently been observed in human bladder carcinomas. A candidate target suppressor gene, p16, was recently identified within this deleted region. In this study, we therefore investigated the loss of heterozygosity (LOH) of the p16 gene which is located on mouse chromosome 4, as well as its expression in mouse bladder carcinomas. We also studied the effects of normal cell contamination on LOH analysis using xenografts in CD-1(ICR) nude mice from B6C3F1 bladder carcinomas. We could not detect any LOH at the p16 locus in the mouse primary bladder carcinomas and xenografts. Surprisingly, overexpression of p16 was found in all primary mouse bladder carcinomas. Using microsatellite polymorphisms, a distinction could be made between PCR products derived from B6C3F1 and CD-1(ICR) nude mice. It was thereby confirmed that effects of normal cell contamination on LOH analysis are negligible when only tumor tissue is carefully sampled. The results suggest that abnormalities of p16 expression may be involved in mouse bladder carcinogenesis, but that gene deletion is not involved.

Animals↗

PubMed2003

[Preliminary study of p16 gene expression in pituitary adenomas].

BACKGROUND & OBJECTIVE: The inactivation and low expression of tumor suppressor gene p16 has been found to play an important role in the tumorigenesis of a wide variety of human tumors, but its association with human pituitary adenomas was not clear. This study was conducted to investigate the relationship between p16 gene expression and clinicopathologic features including invasiveness and recurrence in pituitary adenoma patients. METHODS: The p16 mRNA and p16 protein expression levels were examined using reverse transcription polymerase chain reaction (RT-PCR) and Western Blot analysis respectively in 70 pituitary adenomas and 10 normal brain tissues. RESULTS: Fifty-two of 70 (74.3%) tumor samples presented loss or low p16 mRNA and p16 protein. The invasive and recurrent adenomas had higher loss expression rates than noninvasive and nonrecurrent group respectively; however, there was no significant difference (P >0.05). Moreover, the mean diameter of adenomas without p16 expression was obviously larger than that of p16-positive tumors (22.1+/-7.2 mm versus 8.1+/-4.5 mm, P< 0.01). There was no association between p16 expression and other clinicopathologic features of pituitary adenomas. CONCLUSION: These findings suggested that p16 down-regulation may play an important role in the initial tumorigenesis, growth, and biological behavior of pituitary adenomas.

Adult↗

PubMed2000

[Studies on c-myc gene expression and p16 gene inactivation in nasopharyngeal carcinoma].

OBJECTIVE: The alterations of c-myc and p16 genes and their relationship with the development and progression of nasopharyngeal carcinoma were studied. METHODS: Sixty-nine biopsies of nasopharyngeal carcinoma were examined for the homozygous deletion methylation and reduced expression of p16, and the overexpression of myc family oncogenes using multiple PCR, restriction endonuclease coupled PCR, reverse transcriptase PCR and immunohistochemistry. RESULTS: The homozygous deletion and methylation of p16 gene were found in 7 and 11 cases respectively. The total inactivation rate was 26.1% (18/69). The negative expression of p16, as shown by immunohistochemical examination was found in 42 out of 69 cases (60.9%). The overexpression of myc family oncogenes was found in 51 cases (73.9%). CONCLUSION: It suggests that the inactivation of anti-oncogene p16 and the activation of myc family oncogene may play an important role in the development of nasopharyngeal carcinoma.

Adult↗