Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.
Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines.
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发表时间：
1995-02
期刊：
影响因子：
11.2
通讯作者：
Geoffrey I. Shapiro;Christian D. Edwards;Lester Kobzik;J. Godleski;William G. Richards;D. Sugarbaker;B. Rollins
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文献类型：
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作者：
Geoffrey I. Shapiro;Christian D. Edwards;Lester Kobzik;J. Godleski;William G. Richards;D. Sugarbaker;B. Rollins
cdk4介导的视网膜母细胞瘤易感蛋白（Rb）的磷酸化受到癌基因细胞周期蛋白D1的刺激，并受到候选肿瘤抑制因子p16的抑制。我们研究了这些蛋白质在非小细胞肺癌（NSCLC），这是主要Rb阳性，和小细胞肺癌（SCLC），这是Rb阴性。大多数NSCLC和SCLC切除标本和细胞系过表达细胞周期蛋白D1（表明细胞周期蛋白D1过表达和Rb失活可以在SCLC中共存）。然而，9个Rb阳性NSCLC细胞系中有9个p16缺失或低水平，而Rb阴性NSCLC细胞系和5个SCLC细胞系中有5个p16水平高。在原发性切除标本中，p16在27个NSCLC样本中的18个中未检测到，在5个SCLC样本中的4个中丰富。我们的数据证实了Rb失活和p16表达在一个共同的人类恶性肿瘤之间的预测相互作用，并定义差异p16表达作为NSCLC和SCLC之间的根本区别。
cdk4-mediated phosphorylation of the retinoblastoma susceptibility protein (Rb) is stimulated by cyclin D1, an oncogene, and inhibited by p16, a candidate tumor suppressor. We examined these proteins in non-small cell lung cancer (NSCLC), which is predominantly Rb positive, and small cell lung cancer (SCLC), which is Rb negative. Most NSCLC and SCLC resection specimens and cell lines overexpress cyclin D1 (indicating that cyclin D1 overexpression and Rb inactivation can coexist in SCLC). However, 9 of 9 Rb-positive NSCLC cell lines have absent or low p16, while an Rb-negative NSCLC line and 5 of 5 SCLC cell lines have high levels of p16. In primary resection specimens, p16 was undetectable in 18 of 27 NSCLC samples and abundant in 4 of 5 SCLC samples. Our data confirm the predicted reciprocity between Rb inactivation and p16 expression in a common human malignancy and define differential p16 expression as a fundamental distinction between NSCLC and SCLC.