Expression of p33ING1 mRNA and chemosensitivity in brain tumor cells.
BACKGROUND
Mutations and down-regulation of tumor suppressor genes can contribute to both tumorigenesis and chemotherapy resistance. The tumor suppressor p33ING1 has growth-inhibitory and pro-apoptotic effects recruiting p53 and it plays a role in DNA repair through interaction with PCNA. We questioned whether p33ING1 mRNA expression correlates with the chemosensitivity of brain tumor cells.


METHODS
Various malignant brain tumor cell lines were examined for their sensitivity to cisplatin, doxorubicin, etoposide and the antimitotic agents vincristine and paclitaxel by MTT-cytotoxicity assays. p33ING1 mRNA expression was determined by RT-PCR.


RESULTS
We found that, unlike other tumor types, ING1 levels were higher in glioma cell lines than in normal control cells. Medulloblastoma cells revealed the lowest ING1 expression of the lines tested. Comparing all cell lines, p33ING1 gene expression significantly (p = 0.028) correlated with resistance to vincristine (r2 = 0.87).


CONCLUSIONS
Our results suggest that p33ING1 mRNA levels may be used to predict the chemosensitivity of brain tumor cells to vincristine.
Tallen
G
G
Kinderklinik m. S. Hämatologie/Onkologie, Charité, Campus Virchow Klinikum, Med. Fakultät der Humboldt-Universität Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. gesche.tallen@charite.de
Riabowol
K
K
Wolff
J E
JE
D015415:Biomarkers; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008870:Microtubules / Q000187:drug effects; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009687:Nuclear Proteins; D017239:Paclitaxel / Q000494:pharmacology; D011237:Predictive Value of Tests; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D059004:Topoisomerase I Inhibitors; D025521:Tumor Suppressor Proteins; D014750:Vincristine / Q000494:pharmacology
D015415:Biomarkers; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D059004:Topoisomerase I Inhibitors; D025521:Tumor Suppressor Proteins; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin