Differential roles of p16Ink4a and p19Arf in suppressing gliomagenesis from oligodendrocyte progenitor cells

• Version:1.0 StartHTML:0000000226 EndHTML:0000029504 StartFragment:0000002830 EndFragment:0000029468 SourceURL:file://localhost/Users/nannalindberg/Ctva%20tumor%20suppressors/Manuskript/MS%20Ctva%20knockar%20091013NL.doc CDKN2a encodes the tumor suppressor proteins p16INK4a and p14ARF (p19Arf in mouse) whose functions are frequently lost in human glioblastoma. From previous studies using the RCAS/TV-Atv-a mouse model we have shown that p16Ink4a and p19Arf individually and combined couldan suppress glioma development in Nestin expressing cells (in Ntv-a mice) and in Gfap expressing cells (in Gtv-a mice) (Uhrbom, Dai et al. 2002; Uhrbom, Kastemar et al. 2005; Tchougounova, Kastemar et al. 2007). Recently, we showed that oligodendrocyte progenitor cells (OPCs) could act as cell of origin for glioma by making a Ctv-a mouse in which CNPase expressing cells couldan be targeted by retroviral infection (Lindberg, Kastemar et al. 2009). Here In the current study we have investigated the roles of p16Ink4a and p19Arf in tumor development from OPCs. Unexpectedly, we found that p19Arf only only could suppress oncogene induced gliomagenesis. Loss of Arf caused significantly increased incidence and malignancy of PDGF-B induced tumors and decreased survival compared to Ctv-a wt mice. In addition, Arf deficiency facilitated K-RAS+AKT induced glioma development. Loss of Ink4a, however, lead to nocould not enable tumor induction by (K-RAS++AKT and caused a slight decrease in (PDGF-B) induced tumor incidence. Similarly, wWhen inducing tumors in adult Ctv-a mice we found that Arf loss but not Ink4a loss  enabled tumor induction. Taken together, our data suggest that p19Arf but not p16Ink4a is a tumor suppressor in OPCs of both newborn and adult mice.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Molecular medicine (genetics and pathology)

Molekylär medicin (genetik och patologi)

Molecular Medicine

molekylär medicin (genetik och patologi)

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)