11315

PARK7

DJ-1|DJ1|HEL-S-67p;parkinson protein 7;PARK7;parkinson protein 7

Parkinson disease (autosomal recessive, early onset) 7|epididymis secretory sperm binding protein Li 67p|oncogene DJ1|protein DJ-1|protein deglycase DJ-1

1p36.23

protein-coding

The phosphatidylinositol 3 kinase (PI3K) pathway, which regulates cell survival, is antagonized by the PTEN tumor suppressor. The regulation of PTEN is unclear. A genetic screen of Drosophila gain-of-function mutants identified DJ-1 as a suppressor of PTEN function. In mammalian cells, DJ-1 underexpression results in decreased phosphorylation of PKB/Akt, while DJ-1 overexpression leads to hyperphosphorylation of PKB/Akt and increased cell survival. In primary breast cancer samples, DJ-1 expression correlates negatively with PTEN immunoreactivity and positively with PKB/Akt hyperphosphorylation. In 19/23 primary non-small cell lung carcinoma samples, DJ-1 expression was increased compared to paired nonneoplastic lung tissue, and correlated positively with relapse incidence. DJ-1 is thus a key negative regulator of PTEN that may be a useful prognostic marker for cancer.

The present study was conducted to determine whether any correlation exists between the expression of DJ-1 and WHO grading of the tumor or patient prognosis, and to analyze the function of this oncogene in astrocytomas. Twenty-nine formalin-fixed and paraffin-embedded glioblastomas (grade IV), 21 anaplastic astorocytomas (grade III), and 14 diffuse astrocytomas (grade II) were immunohistochemically studied to identify the expression of DJ-1 protein. The expression of DJ-1 was detected both in the nucleus and cytoplasm of tumor cells; however, such expression varied from case to case. While there was no difference in the cytoplasmic expression of DJ-1 among astrocytomas, its nuclear expression was inversely correlated with the WHO grading of astrocytomas. Moreover, the overall survival of patients with maintained (group 1) or mixed (groups 2 and 3) was significantly longer than those with decreased (group 3) expression (p=0.0063). The present study demonstrated that the survival of patients with astrocytomas was correlated with the nuclear DJ-1 status of the tumor. We herein demonstrated for the first time that the DJ-1 molecule might therefore play an important role as a tumor suppressor in astrocytomas.