title: Downregulation of drs mRNA expression is associated with the progression of adult T-cell leukemia/lymphoma.
abstract: Although adult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-cell leukemia virus (HTLV-1), many other factors are thought to be required for the progression from indolent ATL to aggressive ATLL. The drs gene was originally isolated as a novel suppressor gene of v-src transformation and was shown to induce apoptosis in human cancer cells. To investigate the involvement of drs downregulation in the progression of ATLL, we examined the expression of drs in smoldering, chronic and aggressive ATLL, and found that drs expression was markedly reduced in clinically aggressive ATLL. In aggressive ATLL cell lines, expression of drs mRNA was not detected, although expression of drs mRNA was detected in T-cell lines infected with HTLV-1. A correlation between drs downregulation and expression of the Tax gene was not observed in these T-cell lines. Furthermore, introduction of drs into an ATL cell line, HUT102, by retrovirus vector suppressed the colony formation of the cells in soft agar and enhanced apoptotic cell death of the cells under low serum culture conditions. These results indicate that downregulation of drs is closely linked to the progression of ATLL, independently of Tax expression, suggesting that drs may suppress the progression of ATLL via enhancing apoptosis.
authors.affiliation: Clinical Research Institute, Osaka National Hospital, Chuo-ku, Osaka, Osaka 540-0006, Japan.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Shimakage
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Inoue
authors.forename: Kohichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Kunimitsu
authors.initials: K
authors.lastname: Kawahara
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Oka
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tambe
authors.forename: Kazuta
authors.initials: K
authors.lastname: Yasui
authors.forename: Kayoko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Masuo
authors.initials: M
authors.lastname: Yutsudo
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000473:pathology*; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; C486297:SRPX protein, human