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Inactivation of MMAC1 in bladder transitional-cell carcinoma cell lines and specimens
J Liu1, D C Babaian, M Liebert
1Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Molecular Carcinogenesis
|December 7, 2000
Summary
The MMAC1 gene, a candidate tumor suppressor, showed inactivation in bladder cancer cell lines but not in patient specimens. This suggests another nearby gene may be responsible for bladder transitional-cell carcinoma.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- A candidate tumor suppressor gene was localized to chromosome 10q23.3 in invasive bladder transitional-cell carcinoma (TCC).
- This region contains the MMAC1/PTEN/TEP1 gene (MMAC1), a dual-phosphatase tumor suppressor frequently inactivated in various cancers.
Purpose of the Study:
- To investigate if MMAC1 is inactivated by mutations or deletions in bladder TCC cell lines and specimens.
- To identify the specific tumor suppressor gene responsible for bladder TCC development.
Main Methods:
- Analysis of bladder cancer cell lines and patient tumor specimens.
- Detection of homozygous deletions and mutations within the MMAC1 gene coding region.
Main Results:
- MMAC1 inactivation via homozygous deletions and mutations was observed in 27% (3/11) of bladder cancer cell lines.
- One cell line (UC-3) exhibited homozygous deletions, while two (T-24, UC-9) had missense mutations; T-24 also had a nonsense mutation.
- No mutations or deletions in the MMAC1 coding region were found in 33 bladder TCC patient specimens.
Conclusions:
- MMAC1 is likely not the primary target for inactivation in bladder TCC.
- Another gene located near MMAC1 on chromosome 10q23.3, within a region of frequent allelic loss, may be the actual target gene in bladder TCC development.