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 malignancy, 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.
| Original language | English |
|---|---|
| Pages (from-to) | 107-115 |
| Number of pages | 9 |
| Journal | Journal of Neuro-Oncology |
| Volume | 59 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2002 Sep |
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Keywords
- Gli1
- Gli2
- Gli3
- Gliomas
- Patched
- Smoothened
ASJC Scopus subject areas
- Clinical Neurology
- Cancer Research
- Oncology
- Neuroscience(all)
Cite this
Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy. / Katayama, Masateru; Yoshida, Kazunari; Ishimori, Hisatsugu; Katayama, Makoto; Kawase, Takeshi; Motoyama, Jun; Kamiguchi, Hiroyuki.
In: Journal of Neuro-Oncology, Vol. 59, No. 2, 09.2002, p. 107-115.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy
AU - Katayama, Masateru
AU - Yoshida, Kazunari
AU - Ishimori, Hisatsugu
AU - Katayama, Makoto
AU - Kawase, Takeshi
AU - Motoyama, Jun
AU - Kamiguchi, Hiroyuki
PY - 2002/9
Y1 - 2002/9
N2 - 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 malignancy, 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.
AB - 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 malignancy, 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.
KW - Gli1
KW - Gli2
KW - Gli3
KW - Gliomas
KW - Patched
KW - Smoothened
UR - http://www.scopus.com/inward/record.url?scp=0036713275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036713275&partnerID=8YFLogxK
U2 - 10.1023/A:1019660421216
DO - 10.1023/A:1019660421216
M3 - Article
VL - 59
SP - 107
EP - 115
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 2
ER -