Identification of a candidate gene associated with paclitaxel-resistance and application to a gene therapy in ovarian cancer.
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
Obstetrics and gynecology
|Research Institution||KYUSHU UNIVERCITY |
OGAWA Shinji (2006) Kyushu University, Hospital, Research Associate, 大学病院, 助手 (60380391)
平川 俊夫 (2003-2005) 九州大学, 病院, 講師 (20218770)
KOBAYASHI Hiraoaki Kyushu University, Hospital, Research Associate, 大学病院, 助手 (70260700)
SONODA Kenzo Kyushu University, Hospital, Research Associate, 大学病院, 助手 (30294929)
UEOKA Yousuke Kyushu University, Hospital, Research Associate, 大学病院, 助手 (50372743)
矢幡 秀昭 九州大学, 大学病院, 助手 (30404065)
WAKE Norio Kyushu University, Faculty of Medical Sciences, Professor, 医学研究院, 教授 (50158606)
尼田 覚 九州大学, 病院・助手 (10294919)
小川 伸二 九州大学, 病院・助手 (60380391)
加藤 秀則 九州大学, 生体防御医学研究所, 講師 (60214392)
|Project Period (FY)
2003 – 2006
Completed (Fiscal Year 2006)
|Budget Amount *help
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
|Keywords||paclitaxel resistance / ovarian cancer / cDNA microarray / β-tubulin / 薬剤耐性 / パクリタキセル / マイクロアレイ / ヒト卵巣癌 / In vivo樹立薬剤耐性細胞株|
We established an in vivo paclitaxel-resistant cell line from the parental human ovarian cancer cell lines by repeated paclitaxel administration into tumor-bearing mice. We performed cDNA microarrays between in vivo established paclitaxel-resistant cell line and in vivo established control group to identify the target genes associated with paclitaxel-resistancy. Total RNAs were extracted (1) from in vivo established paclitaxel-resistant cell lines and control group, and (2) from tumor blocks (OM1TX6T and OM1P6T)which were made by subcutaneous transplantion of paclitaxel-resistant cells or control cells.
cDNA were purified and cancer-related gene manifestation profiles which were specifically increased or decreased between two groups were identified. Genes which we used for analysis (1) were 9,063, and the number of the genes which expressed in a resistant cell lines more than double of control cell lines. In addition, genes which we used for analysis (2) were 8,660,and similarly the number of the genes which expressed OM1TX6T more than double of OM1P6T was 298. Now we really push forward extraction of genes related to paclitaxel-resistance from these genes.
On the other hand, overexpression of class III B-tubulin was attracted attention as mechanism of taxane-resistance. We evaluated protein expression level of class I, II, II, IV (IVa+IVb) isotypes of B-tubulin in an ovarian cancer specimens by immunohistochemical stainig, and examined the association with responce to taxane-containing chemotherapy. As a result, in the goup which had chemotherapy with taxane, high expression of class III isotypes of B-tubulin tend to correlate with short prograssion free survival (p=0.081), while this tendency was not found in the group which had chemotherapy without taxane.
Report (5 results)
Research Products (6 results)