Class III β‐tubulin, a marker of resistance to paclitaxel, is overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia

Lee, K. M.; Cao, Dengfeng; Itami, Atsushi; Pour, Parviz M.; Hruban, Ralph H.; Maitra, Anirban; Ouellette, Michel

doi:10.1111/j.1365-2559.2007.02792.x

Cited by 76 publications

(72 citation statements)

References 34 publications

(100 reference statements)

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“…Among the different mechanisms, some are commonly expressed in the tumor tissue. For example, high TUBB3 expression seems to be related to a poor chemotherapy response and adverse prognosis in a wide setting of tumor tissues such as breast (12), stomach (13), pancreas (14), ovary (5), and lung (15). Notably, TUBB3 behaves mainly as a marker of innate resistance because it is not induced after chemotherapy response (5).…”

Section: Discussionmentioning

confidence: 99%

“…Negative control probes for TUBB3 and TUBB were obtained by PCR using the following primers: 5′-AGTGTC-TAAACCCCCGGAGCCAT-3′ (forward) and 5′-AGGTGGG-GAGGACGAGGC-3′ (reverse) as for TUBB3 and 5′-TTCTTACTCCCAAAAAAGAATGAAC-3′ (forward) and 5′-GGAGGAGGGTTCCCCTC-3′ (reverse) as for TUBB. PCR products were cloned in pGEM (Promega) under the T7 promoter and in vitro transcribed using T7 RNA polymerase (Invitrogen), in the presence of 14 C-biotynilated CTP (Invitrogen). After pull down with streptavidin beads, the proteins were run in SDS-PAGE and transferred to poly-(vinylidene fluoride) membranes (Millipore), and Western blotting was done using anti-HuR antibody.…”

Section: Quantitative Reverse Transcriptase Pcr Assay and Ribonucleopmentioning

confidence: 99%

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HuR Regulates β-Tubulin Isotype Expression in Ovarian Cancer

et al. 2010

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The supply of oxygen and nutrients to solid tumors is inefficient because cancer tissues have an inadequate number of microvessels, thus inducing the selective growth of the most aggressive cancer cells. This explains why many of the factors underlying a poor prognosis are induced in hypoxic/hypoglycemic conditions. Among these factors, a prominent role in several solid tumors is played by the class III β-tubulin gene (TUBB3). The study described here reveals that glucose deprivation enhances TUBB3 expression at both the gene and protein levels in A2780 ovarian cancer cells. In silico analysis of TUBB3 mRNA sequence predicted a putative binding site for the RNA-binding protein Hu antigen (HuR) in the 3′ flanking untranslated region. A hypoglycemic-dependent engagement of this site was shown using RNA pull-down and ribonucleoimmunoprecipitation techniques. Thereafter, HuR gene silencing revealed that TUBB3 translation is HuR dependent in hypoglycemia because HuR silencing inhibited the entry of TUBB3 mRNA into cytoskeletal and free polysomes. Finally, the clinical value of this finding was assessed in a clinical cohort of 46 ovarian cancer patients in whom it was found that HuR cytoplasmic staining was associated with high levels of TUBB3 and poor survival. CancerRes; 70(14); 5891-900. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Quantitative Reverse Transcriptase Pcr Assay and Ribonucleopmentioning

confidence: 99%

HuR Regulates β-Tubulin Isotype Expression in Ovarian Cancer

et al. 2010

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“…From in vitro models of resistant cells, multiple mechanisms responsible for the resistant phenotype have been studied. In particular, TUBB3 expression is associated with poor prognosis and resistance to chemotherapy in a variety of cancers, including ovarian (3,4,16), lung (2), gastric (5), breast (6), pancreas (17), and unknown site (18).…”

Section: Discussionmentioning

confidence: 99%

From plasma membrane to cytoskeleton: a novel function for semaphorin 6A

Prislei¹,

Mozzetti²,

Filippetti

et al. 2008

Molecular Cancer Therapeutics

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Class III B-tubulin (TUBB3) overexpression has been reported in ovary, lung, breast, and gastric cancer patients. Currently, no clinical drugs are available for a specific targeting of TUBB3, whereas the investigational drug IDN5390 specifically interacts with TUBB3. To gain insight into the pathways leading to TUBB3 up-regulation, we did a human genome microarray analysis in A2780 cells made resistant to IDN5390 to identify selected pathways specifically disrupted in resistant cells. Using this approach, we discovered that semaphorin 6A (SEMA6A) is down-regulated not only in IDN5390-resistant cells but also in cells made resistant to cisplatin, topotecan, and doxorubicin, whereas no changes were noticed in paclitaxel-and gemcitabine-resistant cells. Acute treatment with IDN5390 was able to down-regulate SEMA6A in cells unselected for drug resistance. TUBB3 expression was assessed in A2780 clones with stable overexpression of SEMA6A and in a panel of clones in which silencing of the protein was obtained. Quantitative PCR was then used to check the modulation of SEMA6A as well as to assess the expression of TUBB3. TUBB3 was increased (median value, 5.4) and reduced (median value, 0.47) in cells with overexpression and silencing of SEMA6A, respectively. Thus, the findings indicate a correlation between the expression of SEMA6A and TUBB3. Then, we found that a form of 83 kDa of SEMA6A is expressed in the cytoskeleton in association with B-actin. These findings suggest for SEMA6A a novel function in the cytoskeleton and a role in modulating tubulin isotype composition and microtubule dynamics.

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“…In addition to neurons, Class III b-tubulin has been detected in selected malignancies, such as in breast cancers and other malignant epithelial tumors (Hasegawa et al 2003;Jirásek et al 2007). Some studies have associated expression of Class III b-tubulin with histologically high grade of malignancy in non-neuronal tumors (Katsetos et al 2003a), and recent studies have described Class III btubulin as a marker of cancer cell resistance to taxanes (Hasegawa et al 2003;Ferlini et al 2005;Lee et al 2007). Expression of Class III b-tubulin has also been shown to represent a useful tool to study early phases of neuronal differentiation in human embryonic development (Easter et al 1993;Katsetos et al 1993Katsetos et al ,2003bKukharskyy et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Class III β-Tubulin Is a Component of the Mitotic Spindle in Multiple Cell Types

Jouhilahti

Peltonen

2008

J Histochem Cytochem.

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S U M M A R Y The findings of this study show that Class III b-tubulin is a component of the mitotic spindle in multiple cell types. Class III b-tubulin has been widely used as a neuronspecific marker, but it has been detected also in association with breast and pancreatic cancers. In this study, we describe a novel finding of Class III b-tubulin in a subpopulation of cells in malignant peripheral nerve sheath tumor. The findings of this study also show that Class III b-tubulin is expressed by normal mesenchymal and epithelial cells (fibroblasts and keratinocytes), two transitional cell carcinoma cell lines, and neurofibroma Schwann cells, as shown by immunolabeling and Western transfer analysis using two different Tuj-1 antibodies that are specific for Class III b-tubulin. The corresponding mRNA was detected using RT-PCR and whole human genome microarrays. Both antibodies localized Class III b-tubulin to the mitotic spindle and showed a colocalization with a-tubulin. The immunoreaction became visible in early prophase, and the most intense immunoreaction was detected during metaphase and anaphase when microtubules were connected to the kinetochores on chromosomes. Class III b-tubulin-specific immunoreaction lasted to the point when the midbody of cytokinesis became detectable.

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Class III β‐tubulin, a marker of resistance to paclitaxel, is overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia

Cited by 76 publications

References 34 publications

HuR Regulates β-Tubulin Isotype Expression in Ovarian Cancer

HuR Regulates β-Tubulin Isotype Expression in Ovarian Cancer

From plasma membrane to cytoskeleton: a novel function for semaphorin 6A

Class III β-Tubulin Is a Component of the Mitotic Spindle in Multiple Cell Types

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