title: Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy.
abstract: Patched (Ptc) is a transmembrane receptor for sonic hedgehog (Shh) and functionally associated with another transmembrane protein, smoothened (Smo). Ptc is a tumor suppressor gene whereas Smo serves as a proto-oncogene of neuroectodermal tumors. Their downstream molecules, Gli1, Gli2, and Gli3, are oncogenes of glioblastomas. We have analyzed mRNA expression of Ptc, Smo, and Gli family members in human astrocytic tumors. The mRNA expression was quantified by real-time polymerase chain reactions in 40 tumors (diffuse astrocytomas; 6 cases: anaplastic astrocytomas; 12 cases: glioblastomas; 22 cases) and four cell lines derived from astrocytic tumors. The MIB-1 proliferating cell indices (PCIs) of these tumors were analyzed by immunohistochemistry. In comparison with the World Health Organization (WHO) classification, the amount of Ptc and Smo mRNAs decreased in proportion to the progression of histological maliganancy, and similar results were obtained with astrocytic tumor-derived cell lines. However, there was no remarkable correlation between the mRNA expression level of each gene and the MIB-1 PCIs. The mRNA expression level of Gli1 was variable and highly elevated in two cases. No remarkable features were found clinically or histologically in these two cases. In summary, our results indicate that Ptc and Smo mRNA levels have an inverse correlation with histological malignancy and suggest that these gene products are implicated in the suppression of astrocytic tumors. In contrast, there was no significant correlation between the mRNA levels of the Gli family members and histological malignancy, suggesting that Gli proteins are not associated with the progression of astrocytic tumors.
authors.affiliation: Developmental Brain Science Group, RIKEN Brain Science Institute, Wako, Saitama, Japan. mkatayama-nsu@umin.ac.jp
authors.forename: Masateru
authors.initials: M
authors.lastname: Katayam
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Ishimori
authors.forename: Makoto
authors.initials: M
authors.lastname: Katayama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawase
authors.forename: Jun
authors.initials: J
authors.lastname: Motoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiguchi
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002648:Child; D005260:Female; D053823:Hedgehog Proteins; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000096:biosynthesis*; D000072079:Patched Receptors; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D000072086:Smoothened Receptor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis*; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D019394:Ki-67 Antigen; C000715470:MAS1 protein, human; D008565:Membrane Proteins; D015513:Oncogene Proteins; D000072079:Patched Receptors; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1