Kokunai T, Tamaki N
Department of Neurosurgery, Kobe University School of Medicine.
Jpn J Cancer Res. 1999 Jun;90(6):638-46. doi: 10.1111/j.1349-7006.1999.tb00795.x.
The role of p21WAF1/CIP1 (p21) in DNA repair and apoptosis following gamma-irradiation remains controversial. In this study the influence of p21 on the radiosensitivity of human brain tumors was investigated. Resected tumors were stained immunohistochemically for p21. Expression of p21 in astrocytic tumors was high, but it was low in medulloblastomas, germinomas, and primary malignant lymphomas. Glioma and medulloblastoma cell lines were transfected with pcDNA/p21 to cause p21 overexpression, then tumor-cell colony formation and apoptosis were assessed following gamma-irradiation of the transfected and nontransfected cells. Overexpression of p21 enhanced clonogenic survival and suppressed apoptosis after gamma-irradiation in human brain tumor cell lines with or without p53 protein deficiency. Radioresistance was acquired when p21 was overproduced in the glioma cell lines irrespective of p53 status.
p21WAF1/CIP1(p21)在γ射线照射后的DNA修复和细胞凋亡中的作用仍存在争议。在本研究中,研究了p21对人脑肿瘤放射敏感性的影响。对切除的肿瘤进行p21免疫组织化学染色。p21在星形细胞瘤中的表达较高,但在髓母细胞瘤、生殖细胞瘤和原发性恶性淋巴瘤中表达较低。用pcDNA/p21转染胶质瘤和髓母细胞瘤细胞系以导致p21过表达,然后在对转染和未转染的细胞进行γ射线照射后评估肿瘤细胞集落形成和细胞凋亡。在有或无p53蛋白缺陷的人脑肿瘤细胞系中,p21的过表达增强了克隆存活并抑制了γ射线照射后的细胞凋亡。无论p53状态如何,当p21在胶质瘤细胞系中过量产生时,都会获得放射抗性。