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Cisplatin-induced genes as potential markers for thyroid cancer
G Lapouge1, R Millon, D Muller
1Laboratoire de Cancérologie Expérimentale et de Radiobiologie, Institut de Recherche contre les Cancers de l'Appareil Digestif, Hôpitaux Universitaires de Strasbourg, B.P. 426, 67091, Strasbourg, France.
Cellular and Molecular Life Sciences : CMLS
|December 25, 2004
Summary
Wild-type p53 status in cells impacts cisplatin sensitivity by altering cell cycle gene expression. Different p53 alterations lead to varied gene regulation, influencing resistance or sensitivity to chemotherapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- The role of p53 in cell cycle arrest and apoptosis following cisplatin treatment is established, but its influence on cellular resistance or sensitivity remains debated.
- Human thyroid papillary carcinoma cell lines with varying p53 statuses (wild-type, mutated, inactivated) were utilized to investigate cisplatin response.
Purpose of the Study:
- To determine how different p53 alterations affect cell cycle gene expression and cisplatin sensitivity in human thyroid papillary carcinoma.
- To identify potential novel biomarkers for advanced thyroid cancer associated with p53 alterations.
Main Methods:
- Quantitative real-time PCR was used to analyze the expression of seven selected cell cycle genes (CDC6-related protein, CCNC, GAS1, TFDP2, MAPK10/JNK3, WEE1, RPA1).
- Gene expression was compared between p53 wild-type, mutated, and inactivated human thyroid papillary carcinoma cell lines after cisplatin treatment.
- Expression levels of these genes were also assessed in human papillary carcinoma tissues.
Main Results:
- Cisplatin treatment upregulated the seven genes in p53 wild-type cells but downregulated them in cells with inactivated p53.
- Cells with mutated p53 showed minimal or no significant effect on the expression of these genes.
- MAPK10/JNK3 was identified for the first time in human thyroid cells and tissue.
- Four genes (CDC6-related protein, CCNC, GAS1, TFDP2) were found to be downregulated in human papillary carcinoma tissues.
Conclusions:
- Different p53 alterations distinctly regulate cell cycle genes, leading to either cisplatin resistance or sensitivity in a defined system.
- GAS1 downregulation in thyroid papillary carcinoma, along with other identified genes, suggests potential as novel biomarkers for advanced thyroid cancers, particularly those with p53 alterations.