Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes.

Kavallaris, Maria; Kuo, D.Y.S.; Burkhart, Catherine; Regl, Donna Lee; Norris, Murray D.; Haber, Michelle; Horwitz, Susan Band

doi:10.1172/jci119642

Cited by 541 publications

(521 citation statements)

References 55 publications

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“…For example, β-tubulin mutation and alterations have been shown to be associated with paclitaxel resistance (Ranganathan et al, 1988(Ranganathan et al, , 1996(Ranganathan et al, , 1998Haber et al, 1995;Giannakakou et al, 1997;Kavallaris et al, 1997Kavallaris et al, , 1999. We have shown that α-tubulin also contributes paclitaxel resistance (Han et al, 1999).…”

Section: Bmentioning

confidence: 50%

“…P-glycoprotein (P-gp), an energy-dependent drug efflux pump shown to confer multidrug resistance (MDR) Pastan, 1988, 1993;Lehnert, 1996;Germann, 1996) 2. alterations in β-tubulin isotypes (Haber et al, 1995;Ranganathan et al, 1988Kavallaris et al, 1997 3. mutations in tubulins (Cabral et al, 1981;Schibler and Cabral, 1986;Giannakakou et al, 1997) 4. up-regulation of caveolin-1 (Yang et al, 1998).…”

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confidence: 99%

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Modulation of paclitaxel resistance by annexin IV in human cancer cell lines

Han¹,

Tahir²,

Cherian³

et al. 2000

Br J Cancer

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Efficacy of paclitaxel in cancer patients has been hampered by the ability of cells to develop paclitaxel resistance (Rowinsky et al, 1992;Rowinsky and Donehower, 1995). Therefore if we understand the mechanism of paclitaxel resistance we will be more successful in the treatment of human cancer. It has been shown that several factors contribute to paclitaxel resistance in vitro:1. P-glycoprotein (P-gp), an energy-dependent drug efflux pump shown to confer multidrug resistance (MDR) Pastan, 1988, 1993;Lehnert, 1996;Germann, 1996) 2. alterations in β-tubulin isotypes (Haber et al, 1995;Ranganathan et al, 1988Kavallaris et al, 1997 3. mutations in tubulins (Cabral et al, 1981;Schibler and Cabral, 1986;Giannakakou et al, 1997) 4. up-regulation of caveolin-1 (Yang et al, 1998.Paclitaxel also activates molecules that are involved in signal transduction pathways such as c-jun N-terminal kinase (Blagosklonny et al, 1995;Wolfson et al, 1997;Wang et al, 1998).Annexins are a family of calcium-dependent phospholipid binding proteins. There are at least 13 annexin family members with a similar structure, characterized by the presence of four or eight repeats of a 70 amino acid motif and a variable N-terminal end (Smith and Moss, 1994;Dubois et al, 1996;Benz-and Hofmann, 1997). Although the roles of the annexins are not well understood, they have been involved in various biological processes including inhibition of phospholipase A2, anticoagulation, endocytosis, exocytosis, inhibition of calcium channels and protein kinase C activity (Smith and Moss, 1994). It was also previously shown that annexin II was elevated in doxorubicin-resistant small-cell lung cancer cell line (Cole et al, 1992). During the course of our antimitotic research, we found that annexin IV was overexpressed in A204197-resistant human colon cancer HCT-15 cells as determined by two-dimensional protein mapping as well as mass spectroscopic analysis. Therefore, we tested whether annexin IV or annexin II was also overexpressed in a paclitaxel-resistant cell line, H460/T800. To our surprise annexin IV, but not annexin II, was overexpressed in the paclitaxel-resistant H460 lung cancer cell line. To further confirm the role of annexin IV in drug resistance, annexin IV cDNA was transfected into 293T cells. Annexin IV transfectants were more resistant to paclitaxel as compared to the vector controls. Thus our study indicates that annexin IV plays a role in regulating paclitaxel resistance. MATERIALS AND METHODS Cell cultureLung cancer cell line NCI-H460 (hereafter referred to as H460) and colon cancer cell line HCT15 were obtained from the American Tissue Culture Collection (ATCC) H460 and HCT15 cells were grown and maintained in RPMI medium plus 10% fetal bovine serum (FBS) or 20% FBS respectively. Paclitaxel-resistant cell lines were derived from the H460 parental cell line. H460 cells were initially selected with IC 50 concentration of paclitaxel and thereafter paclitaxel concentration was doubled every 2-3 weeks until 800 nM paclitaxel resistance was obtain...

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Section: Bmentioning

confidence: 50%

mentioning

confidence: 99%

Modulation of paclitaxel resistance by annexin IV in human cancer cell lines

Han¹,

Tahir²,

Cherian³

et al. 2000

Br J Cancer

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“…These microtubules are also more sensitive to paclitaxel-induced assembly compared to unfractioned tubulin (Lu and Luduena, 1993). Subsequent studies revealed alterations in the expression of specific β tubulin isotypes as result of antimicrotubule drug resistance (Haber et al, 1995;Ranganathan et al, 1996;1998a;1998b;Kavallaris et al, 1997;Kavallaris et al, 1999). In addition, combination studies have shown that cyclosporin A enhances paclitaxel efficacy in lung carcinoma cell lines by modulating β tubulin isotype composition (Ross and Antoniono, 1999).…”

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confidence: 99%

Modulation of endogenous β -tubulin isotype expression as a result of human βIIIcDNA transfection into prostate carcinoma cells

et al. 2001

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In the past several years many laboratories have studied the significance of α and β tubulin proteins in antimicrotubule drug resistance. These studies have extended to several antimicrotubule agents in various carcinoma cell lines. Early studies showed mutations and alterations in the steady state soluble and polymerized α and β tubulin fractions in drug resistant cell lines Cabral et al, 1986;Minotti et al, 1991). Although the existence of different α and β tubulin isotypes and their tissue specific expression was reported in the past, only recently demonstrated were the effects of individual β tubulin isotypes on overall microtubule functions including assembly, dynamics, drug sensitivity and drug binding. Banerjee et al (1990) have shown that β III isotype depleted tubulin assembles into microtubules at a faster rate than unfractioned tubulin. These microtubules are also more sensitive to paclitaxel-induced assembly compared to unfractioned tubulin (Lu and Luduena, 1993). Subsequent studies revealed alterations in the expression of specific β tubulin isotypes as result of antimicrotubule drug resistance (Haber et al, 1995;Ranganathan et al, 1996;1998a;1998b;Kavallaris et al, 1997;Kavallaris et al, 1999). In addition, combination studies have shown that cyclosporin A enhances paclitaxel efficacy in lung carcinoma cell lines by modulating β tubulin isotype composition (Ross and Antoniono, 1999). Recently, Kavallaris et al, (1999) have shown that antisense oligonucleotides to β III isotype sensitized the drug resistant cells to paclitaxel. In addition, mutations in β I isotype were reported in paclitaxel resistant human ovarian carcinoma cells (Giannakakou et al, 1997), breast carcinoma cells (Wiesen and Horwitz, 2000) and non-small-cell lung cancer patients (Monzo et al, 1999) with tumours that were unresponsive to paclitaxel therapy.Antimicrotubule drug resistance associated changes in tubulin isotypes prompted several investigators to determine the contribution of individual isotypes by transfecting cells and examining their antimicrotubule drug response. Wu et al (1998) have shown that transfection of β IVa isotype into human leukemic cell line failed to confer resistance to paclitaxel. Blade et al (1999) have over-expressed rodent β I , β II or β IVb isotypes in CHO cells and shown that these isotypes do not confer resistance to paclitaxel. Our previous work demonstrated increases in β III and β IVa isotypes in human prostate carcinoma cells that were made resistant to estramustine or paclitaxel (Ranganathan et al, 1996(Ranganathan et al, , 1998a. In addition, acute exposures to these agents resulted in elevations of β III levels. To further understand the function of β III isotype in antimicrotubule drug response, parental DU145 human carcinoma cells were transfected with the human β III cDNA. The results presented herein indicate that regulation of tubulin in cells is complex and that attempts to increase levels of a single isotype may lead to compensatory changes in the expression of other isotypes. Sum...

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“…[7][8][9][10] Increased levels of microtubule acetylation and detyrosination have been observed in multiple types of cancer cells, [11][12][13][14][15] and both microtubule-stabilizing and microtubule-destabilizing agents have been widely used in cancer treatment. [16][17][18] However, the clinical applications of these agents have shown the emergence of drug-resistant tumor cells, due to the overexpression of different beta-tubulin isotypes, 19,20 or tubulin mutations. 21 JMJD5 is a member of the JmjC domain-containing protein family, which has been shown to obtain H3K36me2 histone demethylase and hydroxylase activities.…”

Section: Introductionmentioning

confidence: 99%

Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by altering microtubule stability

Wang

et al. 2016

Cell Cycle

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Microtubules play essential roles in mitosis, cell migration, and intracellular trafficking. Drugs that target microtubules have demonstrated great clinical success in cancer treatment due to their capacity to impair microtubule dynamics in both mitotic and interphase stages. In a previous report, we demonstrated that JMJD5 associated with mitotic spindle and was required for proper mitosis. However, it remains elusive whether JMJD5 could regulate the stability of cytoskeletal microtubules and whether it affects the efficacy of microtubuletargeting agents. In this study, we find that JMJD5 localizes not only to the nucleus, a fraction of it also localizes to the cytoplasm. JMJD5 depletion decreases the acetylation and detyrosination of a-tubulin, both of which are markers of microtubule stability. In addition, microtubules in JMJD5-depleted cells are more sensitive to nocodazole-induced depolymerization, whereas JMJD5 overexpression increases a-tubulin detyrosination and enhances the resistance of microtubules to nocodazole. Mechanistic studies revealed that JMJD5 regulates MAP1B protein levels and that MAP1B overexpression rescued the microtubule destabilization induced by JMJD5 depletion. Furthermore, JMJD5 depletion significantly promoted apoptosis in cancer cells treated with the microtubule-targeting anti-cancer drugs vinblastine or colchicine. Together, these findings suggest that JMJD5 is required to regulate the stability of cytoskeletal microtubules and that JMJD5 depletion increases the susceptibility of cancer cells to microtubule-destabilizing agents.

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Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes.

Cited by 541 publications

References 55 publications

Modulation of paclitaxel resistance by annexin IV in human cancer cell lines

Modulation of paclitaxel resistance by annexin IV in human cancer cell lines

Modulation of endogenous β -tubulin isotype expression as a result of human βIIIcDNA transfection into prostate carcinoma cells

Depletion of JMJD5 sensitizes tumor cells to microtubule-destabilizing agents by altering microtubule stability

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