Abstract. Programmed cell death 4 (PDCD4) was recently identified as a novel tumor suppressor gene. The loss of PDCD4 expression was found in several types of human cancer cell lines. To date, however, the status of PDCD4 expression in human glioma tissue is not known. In the present study, the expression of PDCD4 in 30 glioma samples was determined at both mRNA and protein levels by means of RT-PCR, Western blotting, and immunohistochemistry. Herein, we demonstrate, for the first time, that 47% (14/30) of glioma samples lost the expression of PDCD4 mRNA, and 77% (23/30) of glioma samples lacked the PDCD4 protein expression, whereas adjacent normal glial tissues expressed high levels of PDCD4 mRNA and protein. Furthermore, the loss of PDCD4 expression does not significantly correlate with the pathological and clinical features of the glioma. Our new data suggest that the loss of PDCD4 expression is a frequent event in human glioma and may partially contribute to the development of the tumor. IntroductionHuman gliomas are the most common tumor that arises in the central nervous system. As nearly half of gliomas are histologically malignant, therapy of gliomas is one of the most formidable challenges in human malignancies. Over the past two decades, the overall survival of patients suffering from the disease has been improved little, despite therapeutic strategies to employ surgery in combination with radiation and chemotherapy (1,2). Therefore, studies of the molecular biology of the tumor are key issues to getting insight into the mechanisms underlying the pathogenesis of glioma and, in turn, leading to effective therapeutics finally. In recent years, there has been considerable progress in understanding the genetic alterations that cause the initiation and progression of gliomas (3). It is now known that malignant gliomas arise from a number of well-characterized genetic alterations and activations of oncogenes and inactivation of tumor suppressor genes (1). Programmed cell death 4, PDCD4, was recently identified as a novel tumor suppressor gene. To date, however, its role in human glioma is not clear.PDCD4 was first cloned as a gene whose elevated expression is associated with the occurrences of apoptosis in mouse cell lines (4). Subsequently, certain other different mammalian homologues of PDCD4 were identified. So, PDCD4 represents a new pre-apoptotic gene. It is generally accepted that cancer is a disease with deregulated cell proliferation, abnormal differentiation and disturbed apoptosis (5). Thus, it is conceivably inferred that PDCD4 may exert a crucial role in the mechanisms underlying carcinogenesis. Indeed, the following studies demonstrated that PDCD4 was able to inhibit tumor promoter-induced transformation in the mouse JB6 model system (6-8), thereby confirming that PDCD4 acts as a novel tumor suppressor gene. Furthermore, previous studies have shown that PDCD4 exerted its antitumor roles via regulating signal transduction pathways (9,10).Human PDCD4 is first cloned from a human glioma library, wh...