Class III beta-tubulin, a marker of resistance to paclitaxel, is overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia.
OBJECTIVE
Class III beta-tubulin (TUBB3) reduces microtubule stability and confers resistance to microtubule-stabilizing taxanes, including paclitaxel and docetaxel. Pancreatic ductal adenocarcinomas show limited responsiveness to taxanes, but little is known of the underlying mechanisms. The aim of this study was to examine TUBB3 expression in pancreatic cancer cell lines, invasive pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN).


RESULTS
Reverse transcriptase-polymerase chain reaction and Western blot were used to study TUBB3 expression in pancreatic cancer cell lines. Immunohistochemistry was employed to assess TUBB3 in pancreatic cancer specimens, including 75 invasive adenocarcinomas and 41 PanIN precursor lesions. TUBB3 was undetectable in non-neoplastic ducts of the pancreas. In contrast, the vast majority (78-93%) of pancreatic ductal adenocarcinomas demonstrated either diffuse or focal TUBB3 expression. TUBB3 was found to increase progressively in PanIN lesions from 3/16 of PanIN-1 (19%), 5/17 of PanIN-2 (29%) to 5/8 of PanIN-3 lesions (63%).


CONCLUSIONS
TUBB3 is expressed in most pancreatic ductal adenocarcinomas, possibly accounting for the suboptimal response of these tumours to microtubule-stabilizing agents. Up-regulation of TUBB3 in PanIN lesions suggests that microtubule dysfunction is an early feature of this disease. TUBB3 immunohistochemistry could potentially help identify pancreatic cancer patients lacking TUBB3 expression who might benefit from taxane therapy.
Lee
K M
KM
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Cao
D
D
Itami
A
A
Pour
P M
PM
Hruban
R H
RH
Maitra
A
A
Ouellette
M M
MM
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002278:Carcinoma in Situ / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017239:Paclitaxel / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; C498585:TUBB3 protein, human; D014404:Tubulin; D017239:Paclitaxel