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Decreased expression of p57(KIP2)mRNA in human bladder cancer
1Urologische Klinik, Heinrich Heine Universität, Moorenstrasse 5, Düsseldorf, D-40225, Germany.
Abstract:
To identify targets of genetic and epigenetic alterations on chromosome 11p15.5 in human bladder cancer, expression of the imprinted KIP2, IGF2 and H19 genes was studied by quantitative RT-PCR in 24 paired samples of urothelial carcinomas and morphologically normal mucosa obtained by cystectomy, and in bladder carcinoma cell lines. The most frequent alteration in tumour tissue was decreased expression of KIP2 identified in 9/24 (37%) specimens. Decreased IGF2 and H19 mRNA levels were found in five (21%) and three (13%) tumours, respectively. One tumour each overexpressed IGF2 and H19. Loss of H19 expression was only found associated with loss of KIP2 expression, whereas decreased expression of IGF2 mRNA occurred independently. Almost all bladder carcinoma cell lines showed significant changes in the expression of at least one gene with diminished expression of KIP2 mRNA as the most frequent alteration. IGF2 mRNA levels were diminished in several lines, but increased in others. The KIP2 gene could be an important target of genetic and epigenetic alterations in bladder cancer affecting the maternal chromosome 11p15.5. However, reminiscent of the situation in Wilms' tumours, expression of the IGF2 gene on the paternal chromosome can also be disturbed in bladder cancers.
Insights
Genetic and epigenetic alterations in bladder cancer frequently impact KIP2 gene expression on chromosome 11p15.5. The Insulin-like Growth Factor 2 (IGF2) gene also shows altered expression, similar to Wilms' tumors.
Area of Science:
- Genetics
- Epigenetics
- Oncology
Background:
- Chromosome 11p15.5 is a critical region for genomic imprinting.
- Alterations in imprinted genes are implicated in various cancers, including bladder cancer.
Purpose of the Study:
- To investigate genetic and epigenetic alterations of imprinted genes KIP2, IGF2, and H19 in human bladder cancer.
- To identify potential therapeutic targets within the 11p15.5 region.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to analyze gene expression.
- Samples included 24 paired urothelial carcinomas and normal mucosa, plus bladder carcinoma cell lines.
Main Results:
- Decreased KIP2 expression was the most frequent alteration (37%) in tumor tissues.
- Altered IGF2 and H19 expression (decreased or increased) was observed in a subset of tumors and cell lines.
- Loss of H19 expression was associated with KIP2 loss, while IGF2 alterations occurred independently.
Conclusions:
- KIP2 is a significant target of genetic and epigenetic alterations in bladder cancer.
- IGF2 gene expression can also be disturbed in bladder cancers, mirroring findings in Wilms' tumors.