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βIII-Tubulin: A novel mediator of chemoresistance and metastases in pancreatic cancer
- Source :
- Oncotarget
- Publication Year :
- 2015
- Publisher :
- Impact Journals, LLC, 2015.
-
Abstract
- Pancreatic cancer is a leading cause of cancer-related deaths in Western societies. This poor prognosis is due to chemotherapeutic drug resistance and metastatic spread. Evidence suggests that microtubule proteins namely, beta-tubulins are dysregulated in tumor cells and are involved in regulating chemosensitivity. However, the role of beta-tubulins in pancreatic cancer are unknown. We measured the expression of different beta-tubulin isotypes in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Next, we used RNAi to silence beta III-tubulin expression in pancreatic cancer cells, and measured cell growth in the absence and presence of chemotherapeutic drugs. Finally, we assessed the role of beta III-tubulin in regulating tumor growth and metastases using an orthotopic pancreatic cancer mouse model. We found that beta III-tubulin is highly expressed in pancreatic adenocarcinoma tissue and pancreatic cancer cells. Further, we demonstrated that silencing beta III-tubulin expression reduced pancreatic cancer cell growth and tumorigenic potential in the absence and presence of chemotherapeutic drugs. Finally, we demonstrated that suppression of beta III-tubulin reduced tumor growth and metastases in vivo. Our novel data demonstrate that beta III-tubulin is a key player in promoting pancreatic cancer growth and survival, and silencing its expression may be a potential therapeutic strategy to increase the long-term survival of pancreatic cancer patients.<br />National Health and Medical Research Council (NHMRC); Cancer Council New South Wales; Cure Cancer Australia Foundation Grant; Cancer Institute NSW Fellowship; NHMRC CDF Fellowship; NHMRC Senior Research Fellowship
- Subjects :
- Oncology
medicine.medical_specialty
Blotting, Western
Mice, Nude
Apoptosis
macromolecular substances
Biology
Tubulin
Cell Line, Tumor
Pancreatic cancer
Internal medicine
medicine
Animals
Humans
Gene silencing
Anoikis
Pancreatic Cancer
Chemoresistance
Tumor growth
Metastases
Beta III-Tubulin
Neoplasm Metastasis
metastases
Cell Proliferation
Mice, Inbred BALB C
Reverse Transcriptase Polymerase Chain Reaction
Cell growth
Cell Cycle
chemoresistance
Cancer
Cell cycle
medicine.disease
Immunohistochemistry
Xenograft Model Antitumor Assays
βIII-tubulin
ddc
Gene Expression Regulation, Neoplastic
Pancreatic Neoplasms
tumor growth
RNAi Therapeutics
Drug Resistance, Neoplasm
Cell biology
Adenocarcinoma
RNA Interference
CA19-9
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....4d49342269d4b7940be78f193478023c