Downregulation of drs mRNA expression is associated with the progression of adult T-cell leukemia/lymphoma

• Published in: International journal of oncology Vol. 30; no. 6; pp. 1343 - 1348
• Main Authors: SHIMAKAGE, Misuzu, INOUE, Nobumasa, INOUE, Hirokazu, OHSHIMA, Kohichi, KAWAHARA, Kunimitsu, YAMAMOTO, Naoki, OKA, Takashi, TAMBE, Yukihiro, YASUI, Kazuta, MATSUMOTO, Kayoko, YUTSUDO, Masuo
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.06.2007
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Disease Progression; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Human T-lymphotropic virus 1; Humans; In Situ Hybridization; Leukemia, T-Cell - metabolism; Leukemia, T-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, T-Cell - metabolism; Lymphoma, T-Cell - pathology; Male; Medical sciences; Membrane Proteins - biosynthesis; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Tumors; Infection; Cancerology; Messenger RNA; drs; Lymphoproliferative syndrome; Viral disease; Adult T cell leukemia lymphoma; progression; Malignant hemopathy; Non Hodgkin lymphoma; adult T-cell leukemia/lymphoma
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.30.6.1343

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.