Differences in the regulation of intracellular calcium in normal and neoplastic keratinocytes are not caused by ras gene mutations.
Differences in the regulation of intracellular calcium in normal and neoplastic keratinocytes are not caused by ras gene mutations.
复制标题
正常和肿瘤性角质形成细胞中细胞内钙调节的差异不是由 ras 基因突变引起的。
作者：
F. Kruszewski;H. Hennings;R. Tucker;S. Yuspa
对终末分化的抗性的发展是表皮瘤形成的早期事件。可以在体外检测到改变的分化，因为正常表皮细胞在具有大于0.1mM的Ca 2+的培养基中被诱导分化，而用v-rasHa基因转导的肿瘤性表皮细胞和角质形成细胞对Ca 2+具有抗性。在正常表皮细胞中，细胞外Ca 2+（Cao）从0.05 mM升高至1.2 mM导致双相细胞内Ca 2+（Cai）反应，其中瞬时（10 min）峰值为基础值的4-5倍，随后是稳态Cai的持续（大于24 h）2倍增加。Cai的瞬时峰值依赖于血清成分，与Cao无关，而持续的平台期直接依赖于Cao。在1.2 mM Ca 2+中24 h后，正常细胞中对血清因子响应的瞬时峰消失，此时这些细胞正在分化。两种在体内产生良性肿瘤的肿瘤性角质形成细胞系SP-1和308也对Cao的增加具有双相Cai反应。在这些细胞中，瞬时峰也是血清依赖性的，并且比基础值放大10倍。然而，高原值是不持续的，并返回到基础值的8小时，独立于曹。此外，308细胞在1.2 mM Ca 2+中24 h后对血清诱导的Cai瞬变保持敏感。为了确定308和SP-1细胞中激活的c-rasHa突变是否是改变Cai调节的原因，通过缺陷型逆转录病毒将v-rasHa基因引入正常角质形成细胞。这也在体内产生乳头状瘤表型。尽管在1.2 mM Ca 2+中不增殖，但TCFs细胞对Ca（2+）诱导的终末分化具有抗性。正常和v-rasHa角质形成细胞对1.2 mM Ca 2+的反应的Cai曲线是相同的，并且这些细胞在24 h后失去了血清诱导的瞬时Cai峰。因此，c-rasHa基因在308或SP-1细胞中的激活可能不是肿瘤细胞系中改变的Cai反应的唯一原因。Cai的持续生理升高可能与正常和v-rasHa角质形成细胞在1.2 mM Ca 2+中增殖潜力的丧失有关。此外，v-rasHa介导的或激活的c-rasHa介导的互补途径的变化可能有助于肿瘤细胞终末分化的阻滞。
The development of resistance to terminal differentiation is an early event in epidermal neoplasia. Altered differentiation can be detected in vitro since normal epidermal cells are induced to differentiate in medium with Ca2+ greater than 0.1 mM while neoplastic epidermal cells and keratinocytes transduced with a v-rasHa gene are resistant to Ca2+. In normal epidermal cells, the elevation of extracellular Ca2+ (Cao) from 0.05 to 1.2 mM causes a biphasic intracellular Ca2+ (Cai) response in which a transient (10 min) peak of 4-5-fold over basal values is followed by a sustained (greater than 24 h) 2-fold increase in steady-state Cai. The transient peak in Cai is dependent on a serum component and independent of Cao, while the sustained plateau is directly dependent on Cao. The transient peak responding to a serum factor is lost in normal cells after 24 h in 1.2 mM Ca2+, a time when these cells are differentiating. Two neoplastic keratinocyte cell lines, SP-1 and 308, which produce benign tumors in vivo, also have a biphasic Cai response to an increase in Cao. In these cells, the transient peak is also serum dependent and amplified to 10-fold over basal values. However, the plateau value is not sustained and returns to basal values by 8 h, independent of Cao. Furthermore, 308 cells remain sensitive to the serum-induced Cai transient after 24 h in 1.2 mM Ca2+. To determine whether the activating c-rasHa mutation in 308 and SP-1 cells was responsible for the altered Cai regulation, a v-rasHa gene was introduced into normal keratinocytes by a defective retrovirus. This also produces the papilloma phenotype in vivo. Recipient cells were resistant to Ca(2+)-induced terminal differentiation although they did not proliferate in 1.2 mM Ca2+. The Cai profile in response to 1.2 mM Ca2+ was identical in normal and v-rasHa keratinocytes, and these cells lost the serum-induced transient Cai peak after 24 h. Thus, the activation of the c-rasHa gene in 308 or SP-1 cells is probably not solely responsible for the altered Cai response in neoplastic cell lines. Sustained physiological elevation of Cai may be relevant to the loss of proliferative potential in both normal and v-rasHa keratinocytes in 1.2 mM Ca2+. In addition, v-rasHa-mediated or activated c-rasHa-mediated changes in a complementary pathway may contribute to the block in terminal differentiation in neoplastic cells.
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影响因子：
4
作者：
TSIEN, RY;RINK, TJ;POENIE, M
通讯作者：
POENIE, M
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影响因子：
4.8
作者：
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DOI：
10.1111/1523-1747.ep12462536
发表时间：
1988
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Tang,W;Ziboh,VA;Isseroff,R;Martinez,D
通讯作者：
Martinez,D
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DOI：
10.1111/1523-1747.ep12518204
发表时间：
1983
期刊：
The Journal of investigative dermatology
影响因子：
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作者：
O'Keefe,EJ;PayneJr,RE
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PayneJr,RE
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DOI：
10.1177/32.10.6384359
发表时间：
1984
期刊：
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
影响因子：
--
作者：
Brewer,LM;Durkin,JP;MacManus,JP
通讯作者：
MacManus,JP