Mutational analysis of the beta-tubulin gene in lung cancer.
Recently, several studies have suggested that a major mechanism of resistance to paclitaxel might involve mutations in the beta-tubulin gene in tumor cells. To investigate the frequency of beta-tubulin mutations in Japanese patients with small and non-small cell lung cancer, direct sequence analysis following reverse transcription-polymerase chain reaction (RT-PCR) of the beta-tubulin gene was performed using total RNA from 20 lung cancer cell lines and 22 specimens from lung cancer patients. First-strand cDNA sequence analysis of the 42 samples showed silent mutations at codon 180 of the beta-tubulin gene, which encodes the GTP-binding site of the protein, and codons 195 and 217. However, neither missense nor non-sense mutations affecting microtubule dynamics, within or near the GTP-binding site of the beta-tubulin gene, were detected. These results indicate that beta-tubulin gene mutations might not play a major role in the mechanism of resistance to paclitaxel in Japanese lung cancer patients. Further investigations are needed to clarify the mechanism of drug resistance.
Tsurutani
Junji
J
Fourth Department of Internal Medicine, Kinki University School of Medicine, Ohonohigashi 377-2, Osakasayama, 589-8511, Osaka, Japan.
Komiya
Takefumi
T
Uejima
Hisao
H
Tada
Hirohito
H
Syunichi
Negoro
N
Oka
Mikio
M
Kohno
Shigeru
S
Fukuoka
Masahiro
M
Nakagawa
Kazuhiko
K
D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014404:Tubulin / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000502:physiology*
D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014404:Tubulin