C-KIT overexpression and mutation in nasopharyngeal carcinoma cell lines and reactivity of Imatinib on these cell lines.
OBJECTIVE
We previously reported that C-KIT overexpression and mutation exist in biopsy samples of nasopharyngeal carcinoma (NPC). Yet whether Imatinib had an inhibitory effect on the proliferation of NPC in vitro was still unknown. So, this study examined whether sensitivities to Imatinib of other cell lines are different and whether C-KIT expression and mutations exist, to analyze the correlations between them.


METHODS
The expression of C-KIT in NPC cell lines, including CNE-1, CNE-2, Hone-1, C-666, SUNE-1, 5-8F, and nasopharyngeal epithelial (NPE) cell line NP-69, were detected by Western blot. Direct sequencing of polymerase chain reaction (PCR) products was performed to analyze the sequences of C-KIT from the above-mentioned cell lines. Inhibitory effects on proliferation by Imatinib on these cell lines were determined by CCK-8 assay. Pearson product moment correlation and t test were used to analyze the correlation betweeen C-KIT overexpression, C-KIT gene mutation, and the inhibitory effect of Imatinib.


RESULTS
Compared with NPE cell line NP-69, NPC cell lines CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F had significantly higher levels of C-KIT expression. Heterozygous IVS17+78T>C were found in CNE-1, CNE-2, Hone-1, and NP-69 cell lines, homozygous IVS17+78T>C was found in C-666, and no mutation was found in SUNE-1 or 5-8F. Imatinib had a dose-dependent inhibitory effect on proliferation for CNE-1, CNE-2, Hone-1, C-666, SUNE-1, and 5-8F. No significant correlation between the inhibitory effects of Imatinib, C-KIT overexpression, or C-KIT mutation was found.


CONCLUSIONS
C-KIT overexpression and intron mutation were found in NPC cell lines and Imatinib had a dose-dependent inhibitory effect on proliferation for NPC cell lines, yet no significant correlation between C-KIT overexpression, C-KIT mutation, or the inhibitory effect of Imatinib was found.
Huang
Pei-Yu
PY
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, PR China.
Hong
Ming-Huang
MH
Zhang
Xing
X
Mai
Hai-Qiang
HQ
Luo
Dong-Hua
DH
Zhang
Li
L
D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D000068877:Imatinib Mesylate; D007438:Introns; D009154:Mutation; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D009305:Nasopharynx / Q000166:cytology; D010879:Piperazines / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit