Analysis of p18^INK4C in adult T‐cell leukaemia and non‐Hodgkin's lymphoma

Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL)

“…166 Expression of p18 was often undetectable in HTLV-I-associated cell lines whereas it was expressed in normal CD4 + T cells, HTLV-I noninfected leukemia/lymphoma cell lines, and purified leukemic cells from HTLV-I uninfected acute leukemia patients. 69,[167][168][169] These results suggest that inactivation of p18 may be peculiar to ATLL. Further studies of expression of p18 in fresh ATLL cells will also be of interest.…”

“…36,[179][180][181] However, p18 mRNA is detected in several tax expressing cell lines: ATL-1K (HTLV-I infected cell line) and the stably tax transfected Jurkat cell lines. 167 In addition, decrease of p18 mRNA expression is more obvious in HTLV-I infected than in Taximmortalized T cells, 69 so Tax may not be the only determinant decreasing the expression of p18. Furthermore, while Tax repression may be important for the early carrier phase, it is probably not very relevant for the later phase of the disease when most of the HTLV-I infected cells no longer express Tax.…”

“…Aberrations of CDKIs, Rb, and p53 in ATLL as examined by Hangaishi et al 148 and ourselves 90,103,167,202,230 are summarized in Table 3. Because of the short distance between p15 and p16, both genes are often co-deleted and can be thought of as a group.…”

Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response

“…Alteration of the p53 gene has been observed in 40% of ATL cases (Kinoshita et al, 1992;Sakashita et al, 1992;Yamato et al, 1993), while alterations in p15 INK4B , p16 INK4A , and retinoblastoma (Rb) genes occur in about 30, 35, and 5% of ATL cases, respectively (Hatta et al, 1997a;Suzuki et al, 1999a;Hatta and Koeffler, 2002). Although rare, mutation of p18 INK4C has also been identified in some ATL cells (Hatta et al, 1997b).…”

Activation of protein kinase C promotes human cancer cell growth through downregulation of p18INK4c

“…On the other hand, a number of studies suggested that genetic alterations of p18 INK4c gene are rare events in human tumors Otsuki et al, 1996;Rusin et al, 1996;Hatta et al, 1997). However, it was recently reported that treatment of p18 INK4c null and heterozygous mice with a chemical carcinogen causes tumor at an accelerated rate (Bai et al, 2003 As shown by Western and Northern blot analysis, 12-O-tetradecanoylphorbol-13-acetate (TPA), widely used as a PKC activator (Nishizuka, 1984), treatment of both human embryonic kidney (HEK) 293 T cells and human colon carcinoma HCT116 cells resulted in significant time-and dose-dependent downregulation of p18 INK4c protein and its mRNA (Figure 1).…”