Expression of the apoptosis inhibitor, survivin, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line.
Expression of the apoptosis inhibitor, survivin, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line.
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发表时间：
1999-09
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通讯作者：
D. Grossman;J. McNiff;Fengzhi Li;D. Altieri
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作者：
D. Grossman;J. McNiff;Fengzhi Li;D. Altieri
最近描述的凋亡抑制剂生存素在许多人类癌症中表达，因此可能有助于疾病进展和对治疗的抵抗。它在非黑色素瘤皮肤癌中的潜在作用尚不清楚。通过免疫组化，生存素表达在81%（17/21）的基底细胞癌（BCC）的结节和Morpheaform亚型，并在92%（24/26）的皮肤鳞状细胞癌（SCC）。生存素也表达在19个癌前病变的Bowen病（SCC原位）和肥大性光化性角化病（HAK），这表明它的外观发生在角质形成细胞转化早期。Western blotting检测Survivin在角质形成细胞HaCat中的表达。用绿色荧光蛋白（GFP）缀合的生存素反义或GFP缀合的生存素显性负突变体（Cys 84 Ala）转染HaCat细胞导致在没有其他遗传毒性刺激的情况下自发凋亡。在GFP结合的生存素反义转染，内源性生存素的水平下降，通过流式细胞术证实。这与对应于凋亡细胞的亚G 0/G1级分的5倍增加和具有4 N DNA含量的增殖细胞的减少有关。这些数据表明，凋亡抑制生存素可能参与BCC和SCC的发病和进展，并表明，治疗靶向生存素可能是有益的复发性或晚期疾病的患者。
The recently described apoptosis inhibitor survivin is expressed in many human cancers, thus potentially contributing to disease progression and resistance to therapy. Its potential role in nonmelanoma skin cancer is unknown. By immunohistochemistry, survivin was expressed in 81% (17 of 21) of basal cell carcinomas (BCC) of both nodular and morpheaform subtypes, and in 92% (24 of 26) of cutaneous squamous cell carcinomas (SCC). Survivin was also expressed in 19 premalignant lesions of Bowen's disease (SCC in situ) and hypertrophic actinic keratosis (HAK), suggesting that its appearance occurs early during keratinocyte transformation. Survivin expression was detected by Western blotting in a model keratinocyte cell line, HaCat. Transfection of HaCat cells with green fluorescent protein (GFP)-conjugated survivin antisense or GFP-conjugated survivin dominant negative mutant (Cys84Ala) resulted in spontaneous apoptosis in the absence of other genotoxic stimuli. In GFP-conjugated survivin antisense transfectants, a decreased level of endogenous survivin was confirmed by flow cytometry. This was associated with a five-fold increase in the sub-G0/G1 fraction corresponding to apoptotic cells and a decrease in proliferating cells with 4N DNA content. These data demonstrate that apoptosis inhibition by survivin may participate in the onset and progression of both BCC and SCC, and suggest that therapeutic targeting of survivin may be beneficial in patients with recurrent or advanced disease.