Expression and growth-promoting effect of adult t-cell leukemia-derived factor a human thioredoxin homologue in hepatocellular carcinoma

Nakamura, Hajime; Masutani, Hiroshi; Tagaya, Yutaka; Yamauchi, Akira; Inamoto, Takashi; Nanbu, Yoshihiko; Fujii, Shingo; Ozawa, Kazue; Yodoi, Junji

doi:10.1002/1097-0142(19920415)69:8<2091::aid-cncr2820690814>3.0.co;2-x

Cited by 130 publications

(61 citation statements)

References 20 publications

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“…Positive tumor cells were quantified by evaluating at least 1,000 cells and were expressed as percentage. Hepatocellular carcinoma tissue was used as positive control for thioredoxin (15,23). In immunohistochemistry for thioredoxin, parallel incubation with normal mouse serum instead of a mouse monoclonal antibody against thioredoxin was also done to rule out the nonspecific staining (negative control).…”

Section: Methodsmentioning

confidence: 99%

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

Kim

Miyoshi

Taguchi

et al. 2005

Clinical Cancer Research

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164

115

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Purpose: Thioredoxin overexpression is suggested to be associated with resistance to several chemotherapeutic agents in vitro. In the present study, it has been studied whether or not high thioredoxin expression is associated with resistance to docetaxel therapy in breast cancer patients. Patients and Methods: Sixty-three primary breast cancer patients were treated with docetaxel (60 mg/m 2 , q3w) for four cycles in the neoadjuvant setting. Expression of thioredoxin, estrogen receptor (ER), p53, BRCA-1, and Bcl-2 in tumor tissues obtained before docetaxel therapy was studied by immunohistochemistry (thioredoxin, p53, BRCA-1, and Bcl-2) and enzyme immunoassay (ER), and relationship of expression of these biomarkers with a pathologic response was investigated.Results: There was no significant correlation between the expression of p53, BRCA-1, or Bcl-2 and a response to docetaxel. However, tumors with high thioredoxin expression showed a significantly lower response rate (0%) than those with low thioredoxin expression (30.6%; P = 0.018) and ER-negative tumors showed a significantly higher response rate (32.4%) than ER-positive tumors (10.7%; P = 0.043).Thioredoxin expression significantly increased after docetaxel therapy (mean, 56.1%) as compared with that before docetaxel therapy (mean, 28.6%; P < 0.0001) but there was no significant association between the extent of increase in thioredoxin expression and response. Conclusion: High thioredoxin expression in prechemotherapy tumor samples, but not the increase in thioredoxin expression induced by docetaxel, is associated with resistance to docetaxel in breast cancer.Thioredoxin and ER might be clinically useful in the prediction of a response to docetaxel. Docetaxel, which belongs to taxanes, is one of the most powerful anticancer drugs for breast cancer, and an increasing number of breast cancer patients have been treated with docetaxel not only in the metastatic setting but also in the adjuvant setting, and more recently, in the neoadjuvant setting. The response rate of docetaxel, however, is f50% even in the first-line chemotherapy and it decreases to 20% to 30% in the second-or third-line chemotherapy (1 -3). Therefore, it is of vital importance to select the patients who are very likely to respond to docetaxel to eliminate the unnecessary treatment.

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Section: Methodsmentioning

confidence: 99%

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

Kim

Miyoshi

Taguchi

et al. 2005

Clinical Cancer Research

Self Cite

164

115

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“…RAR␥ inhibits proliferation and activates apoptosis in breast cancer cells (Fanjul et al, 1996;Raffo et al, 2000). VDUP1 suppresses cell proliferation by inhibiting the reducing potential of the disulfide-reducing protein thioredoxin and by downregulating thioredoxin expression (Nakamura et al, 1992(Nakamura et al, ,1997Nishiyama et al, 1999). Expression of VDUP1 is downregulated in chemically induced rat mammary tumors (Yang et al, 1998).…”

Section: Differential Gene Regulation By Glucocorticoids and Progementioning

confidence: 99%

Overlapping but Distinct Profiles of Gene Expression Elicited by Glucocorticoids and Progestins

Wan

Nordeen

2003

Recent Progress in Hormone Research

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Glucocorticoids and progestins bind to receptors that share many structural and functional similarities, including virtually identical DNA recognition specificity. Nonetheless, the two hormones mediate very distinct biological functions. For example, progestins are associated with the incidence and progression of breast cancer, whereas glucocorticoids are growth suppressive in mammary cancer cells. To understand the mechanisms that engender biological specificity, we have employed two systematic approaches to identify genes that are differentially regulated by the two hormones. The first strategy is to utilize Affymetrix oligonucleotide arrays to compare glucocorticoid-and progestinregulated gene expression in a human breast cancer cell line. This global analysis reveals that the two hormones regulate overlapping but distinct sets of genes, including 31 genes that are differentially regulated. Surprisingly, the set of differentially regulated genes was almost as large as the set of genes regulated by both hormones. Examination of the set of differentially regulated genes suggests mechanisms behind the distinct growth effects of the two hormones in breast cancer. The differential regulation of four genes representing different regulatory patterns was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analyses. Treatment with cycloheximide or mifepristone (RU486) indicates that the regulation is a primary, receptor-mediated event. The second strategy is to employ a retroviral promoter trap and Cre/loxP-mediated, sitespecific recombination to identify genes that are differentially regulated by glucocorticoids and progestins. A mouse fibroblast cell line (4F) stably expressing both glucocorticoid receptor (GR) and progesterone receptor (PR) and containing a single copy of a multifunctional selection plasmid was generated. This line was transduced with a self-inactivating retroviral promoter trap vector carrying coding sequences for Cre-recombinase (Cre) in the U3 region. Integration of the provirus places Cre expression under the control of genomic flanking sequence. Activation of Cre expression from integration into active genes results in a permanent switch between the selectable marker genes that convert the cells from neomycin resistant to hygromycin resistant. Selection for hygromycin resistance after hormone treatment yields recombinants in which Cre sequences in the U3 region are expressed from hormone-inducible, upstream cellular promoters. Because Cre-mediated recombination is a permanent event, the expression of the selectable marker genes is independent of ongoing Cre expression. Thus, this system permits the identification of genes that are transiently or weakly induced by hormone. Detailed analyses of genes identified in these studies will furnish a mechanistic understanding of differential regulation by glucocorticoids and progestins.

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“…15 Trx up-regulates IL-2 receptors in leukemic T cells. 16 Moreover, Trx promotes cell growth of several malignant cell types, specifically, liver cell lines (PLC/ PRF/5), Burkitt lymphoma cell lines (BL41), lymphoblastoid cell lines (CRAG8, CRB 95, 1G8), or chronic lymphocytic leukemia (CLL) cells, [17][18][19] and prevents apoptosis via direct binding interaction of the reduced form with apoptosis signalregulating kinase (ASK) 1. ASK1 is a kinase that is required for apoptosis induced by tumor necrosis factor-␣ (TNF-␣).…”

Section: Introductionmentioning

confidence: 99%

Truncated thioredoxin (Trx80) induces production of interleukin-12 and enhances CD14 expression in human monocytes

Pekkari¹,

Avila‐Cariño²,

Bengtsson³

et al. 2001

Blood

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Expression and growth-promoting effect of adult t-cell leukemia-derived factor a human thioredoxin homologue in hepatocellular carcinoma

Cited by 130 publications

References 20 publications

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

High Thioredoxin Expression Is Associated with Resistance to Docetaxel in Primary Breast Cancer

Overlapping but Distinct Profiles of Gene Expression Elicited by Glucocorticoids and Progestins

Truncated thioredoxin (Trx80) induces production of interleukin-12 and enhances CD14 expression in human monocytes

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