1.
Asp, Julia, 1973, et al.
(författare)
Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma.
2001
Ingår i: Journal of orthopaedic research : official publication of the Orthopaedic Research Society. - 0736-0266. ; 19:1, s. 149-54
Tidskriftsartikel (refereegranskat) abstract
The G1 regulatory pathway involving p16, pRb and cdk4 in the cell cycle has been investigated in human chondrosarcoma. The protein expression of p16, pRb and cdk4 was analyzed by Western blot in cultured cells from eight chondrosarcomas and in two chondrosarcoma cell lines. Both cell lines and one other sample were negative for p16. Moreover, one of the cell lines was pRb-negative and showed a high expression of cdk4 as well. In the other cell line and in three other samples pRb of expected size were detected in addition to a shorter form of the protein. To further investigate the reasons for down-regulation of the p16 protein, the p16-coding gene CDKN2 was analyzed by polymerase chain reaction (PCR), methyl-specific PCR (MSP) and sequencing in all tumor samples as well as in corresponding tumor tissues from three of the samples. The p16-negative samples were all found to have homozygous deletion of CDKN2. Another sample showed partial gene methylation and a heterozygous position in codon 148 was detected in one sample. The same base substitution was also found in two of the tissue samples. Finally, cytogenetic analysis of the samples with homozygously deleted CDKN2 revealed multiple structural abnormalities in all three cases. In conclusion, the p16/pRb/cdk4 pathway may play an important role in the pathogenesis of some chondrosarcomas.
2.
Asp, Julia, 1973, et al.
(författare)
Changes in p14(ARF) do not play a primary role in human chondrosarcoma tissues.
2001
Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 93:5, s. 703-5
Tidskriftsartikel (refereegranskat) abstract
The locus encoding the tumor suppressor p16 has been found to code for a second, different protein. This protein, p14(ARF), has been shown to protect p53 from degradation. Like p16, its gene is often altered in different cancers. In this study, the first unique exon, exon 1 beta, of p14(ARF), has been studied in 22 chondrosarcoma tissues using polymerase chain reaction, DNA sequencing and methylation-specific polymerase chain reaction. One chondrosarcoma was found to have exon 1 beta homozygously deleted, but neither mutations nor methylations were found in any of the chondrosarcomas. This indicates that genetic changes of p14(ARF) are a rare event in chondrosarcoma.
3.
Asp, Julia, 1973, et al.
(författare)
Changes of the p16 gene but not the p53 gene in human chondrosarcoma tissues.
2000
Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 85:6, s. 782-6
Tidskriftsartikel (refereegranskat) abstract
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.
