Expression of the Gfi-1 gene in HTLV-1-transformed T cells.
Human T-cell leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and immortalizes human T cells interleukin-2 (IL-2)-dependently in vitro. Protracted culture of HTLV-I-infected T cells enables them to grow IL-2-independently. Although acquisition of IL-2-independent growth has been correlated with activation of signal transducers and activators of transcription (STATs), the precise mechanism of IL-2-independent growth is unknown. We found that expression of the Gfi-1 (growth factor independence-1) gene was elevated in most HTLV-I-transformed IL-2-independent cell lines but in few HTLV-I-infected IL-2-dependent cell lines. We also found elevated expression of Gfi-1 in fresh leukemic cells of ATLL patients. Although expression of Gfi-1 is correlated with activation of STAT3, induction of the dominant negative form of STAT3 in the HUT102 cell line does not alter the level of Gfi-1 expression. Furthermore, MT2 cells treated with Gfi-1 antisense oligonucleotide had reduced [3H]thymidine uptake compared with MT2 cells treated with Gfi-1 sense oligonucleotide. These findings indicate that Gfi-1 activation is involved in the IL-2-independent growth of HTLV-I-transformed T cells in vitro and in the development of ATLL in vivo, but is not induced by STAT activation.
Sakai
I
I
First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan. ikusakai@m.ehime-u.ac.jp
Yamauchi
H
H
Yasukawa
M
M
Kohno
H
H
Fujita
S
S
D000328:Adult; D000368:Aged; D002461:Cell Line, Transformed / Q000821:virology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015368:Human T-lymphotropic virus 1 / Q000254:growth & development*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D029701:Saccharomyces cerevisiae Proteins; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C064055:ABFI protein, S cerevisiae; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors