IL-2 independent transformation of a unique human T cell line, TY8-3, and its subclones by HTLV-I and -II

“…These cells were treated with mitomycin C as described previously. 22 They were cocultured with the IL-2 dependent human T-cell line, TY8-3, 27 established from a thymoma specimen from a patient with myasthenia gravis, in RPMI-1640 medium containing 10% FBS and 10 ng/ml IL-2. After growing cells were expanded, the cells were maintained in the absence of IL-2.…”

Section: Cocultivation Of Interleukin 2 (Il-2) Dependent Ty8-3 and Htmentioning

confidence: 99%

Constitutive expression of the cyclooxygenase-2 gene in T-cell lines infected with human T cell leukemia virus type I

Mori

Inoue

Yoshida³

et al. 2001

Int. J. Cancer

Self Cite

View full text Add to dashboard Cite

Cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes the formation of prostaglandins and other eicosanoids from arachidonic acid, is constitutively expressed in several human carcinomas. COX-2 expression, however, has not been extensively studied in leukemia. Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia, an aggressive form of human T cell malignancy. We studied COX-2 mRNA expression in various human Tcell lines. Northern blot analysis revealed that COX-2 mRNA steady-state levels were high in 4 of 7 T-cell lines infected with HTLV-I. COX-2 mRNA, however, was not expressed in any of 3 HTLV-I-negative T-cell lines. We also confirmed COX-2 expression in 6 of 7 HTLV-I-positive T-cell lines by reverse transcription-PCR. HTLV-I Tax is known to increase the expression of cellular genes and thus we assayed Tax for its ability to increase transcription from the COX-2 promoter. Although Tax increased transcription of the COX-2 promoter in a T-cell line, Tax expression did not induce COX-2 mRNA expression, indicating that Tax alone is not sufficient for significant accumulation of COX-2 mRNA, which probably requires an additional viral protein. To evaluate the potential role of COX-2 in T cells, the HTLV-Iinfected T-cell lines were treated with NS398, a selective COX-2 inhibitor. NS398 treatment inhibited proliferation and induced apoptosis of HTLV-I-infected T-cell lines and downregulated Bcl-2 and Bcl-x L mRNA expression, followed by chromosomal DNA fragmentation. Our data suggest that COX-2 is expressed selectively in T-cell lines infected with HTLV-I and that this gene may play a role in cell survival.

show abstract

“…MT-2, MT-4, TY8-3/MT-2, 27 TY8-3/TCL-Kan, 27 HUT-102 and SLB-1 are HTLV-I-infected transformed T-cell lines. ILT-8M2 28 was obtained from a HTLV-I-infected carrier.…”

Section: Cell Lines and Cell Growth Assaymentioning

confidence: 99%

“…TL-OmI, ED-40515 and C5MJ are HTLV-I-infected leukemic T-cell lines. TY8-3, 27 Jurkat and MOLT-4 are HTLV-I-negative T-cell lines. JPX-9 29 and JPX-9/M 30 lines are derivatives of Jurkat cells and possess stably integrated Tax or a mutant Tax under the control of a metallothionein promoter, respectively.…”

Section: Cell Lines and Cell Growth Assaymentioning

confidence: 99%

Human T‐cell leukemia virus type‐I Tax induces expression of interleukin‐6 receptor (IL‐6R): Shedding of soluble IL‐6R and activation of STAT3 signaling

Horiuchi

Yamamoto

Dewan

et al. 2006

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Human T‐cell leukemia virus type‐I (HTLV‐I) encodes for the viral protein Tax, which is known to significantly disrupt transcriptional control of cytokines, cytokine receptors and other immuno‐modulatory proteins in T cells. Specific dysregulation of these factors can alter the course and pathogenesis of infection. Soluble interleukin‐6 receptor (sIL‐6R) was shown to circulate at elevated levels in HTLV‐I‐infected patients, and high expressions of IL‐6R and sIL‐6R by HTLV‐I‐infected T cells were clinically and experimentally associated with Tax activity. To examine roles of Tax in expression of the IL‐6R gene, the JPX‐9 cell line was used, which is derived from Jurkat cell line expressing Tax cDNA. Over‐expression of Tax enhanced IL‐6R expression but not in Tax mutant JPX‐9/M cell line. The clinical relevance of these observations was further demonstrated by ELISA using sera obtained from HTLV‐I‐infected patients. Our results revealed that sIL‐6R levels were apparently elevated in HAM/TSP patients who were expressing Tax in their cells, while ATL patients' cells barely expressed Tax. HTLV‐I‐infected T‐cell lines stimulated by IL‐6/sIL‐6R showed gp130‐mediated STAT3 activity. IL‐6/sIL‐6R enhanced proliferation of HTLV‐I‐infected T cells in association with activation of STAT3. Consequently, Tax‐mediated regulations of IL‐6R and sIL‐6R observed in HTLV‐I‐associated disorders may contribute to proliferation of HTLV‐I‐infected T cells through activation of inducible STAT3, and ultimately affect malignant growth and transformation of T cells by HTLV‐I. © 2006 Wiley‐Liss, Inc.

show abstract

IL-2 independent transformation of a unique human T cell line, TY8-3, and its subclones by HTLV-I and -II

Cited by 11 publications

References 60 publications

Overexpression of caveolin-1 in adult T-cell leukemia

Overexpression of caveolin-1 in adult T-cell leukemia

Constitutive expression of the cyclooxygenase-2 gene in T-cell lines infected with human T cell leukemia virus type I

Human T‐cell leukemia virus type‐I Tax induces expression of interleukin‐6 receptor (IL‐6R): Shedding of soluble IL‐6R and activation of STAT3 signaling

Contact Info

Product

Resources

About