Rubin A L, Rice R H
Cancer Res. 1986 May;46(5):2356-61.
In five lines of cultured human squamous carcinoma cells, transglutaminase activity and envelope competence were highly sensitive to retinoic acid and calcium levels in the growth medium. In cells grown in low calcium medium, these measures of keratinocyte differentiation were reduced. Retinoic acid suppressed envelope competence but total transglutaminase activity was markedly reduced, slightly affected, or greatly stimulated depending upon the cell line and whether the cells were grown in low calcium or 1.8 mM calcium-containing medium. Examination by anion exchange chromatography of the transglutaminase activity in SCC-12B2 cultures showed that expression of the particulate form (type I) of the enzyme was greatly stimulated by calcium. The increase in this activity to high levels that occurs at confluence could be almost completely suppressed by retinoic acid in the medium. The soluble form (type II) in the SCC-12B2 cells was induced in growing or confluent cultures by retinoic acid independent of the calcium concentration in the medium, but the 50% effective concentration (100 nM) for its stimulation was approximately 50-fold higher than the 50% effective concentration for suppression of the type I enzyme (2 nM). Thus, these enzymes appear to be distinct and independently regulated. This conclusion is supported by the finding that SCC-4 and SCC-9 almost exclusively expressed types II and I forms, respectively. In contrast to the results with neoplastic cells, in cultured normal epidermal cells type I enzyme comprised the overwhelming majority of activity and was only partially (75-90%) suppressible by retinoic acid, while type II enzyme seemed poorly if at all stimulable. Thus, the SCC lines appear appropriate for studying biochemical mechanisms of action of certain physiological agents, the molecular basis for altered regulation of differentiated function in neoplastic cells, and the origin of diversity within tumors.
在培养的人鳞状癌细胞的五个细胞系中，转谷氨酰胺酶活性和包膜形成能力对生长培养基中的视黄酸和钙水平高度敏感。在低钙培养基中生长的细胞中，这些角质形成细胞分化指标降低。视黄酸抑制包膜形成能力，但总转谷氨酰胺酶活性根据细胞系以及细胞是在低钙培养基还是含1.8 mM钙的培养基中生长而显著降低、略有影响或受到极大刺激。通过阴离子交换色谱法检测SCC - 12B2培养物中的转谷氨酰胺酶活性表明，该酶的颗粒形式（I型）的表达受到钙的极大刺激。在汇合时该活性增加到高水平，培养基中的视黄酸几乎可以完全抑制这种增加。SCC - 12B2细胞中的可溶性形式（II型）在生长或汇合培养物中由视黄酸诱导，与培养基中的钙浓度无关，但其刺激的50%有效浓度（100 nM）比抑制I型酶的50%有效浓度（2 nM）高约50倍。因此，这些酶似乎是不同的且受独立调节。这一结论得到以下发现的支持：SCC - 4和SCC - 9几乎分别只表达II型和I型。与肿瘤细胞的结果相反，在培养的正常表皮细胞中，I型酶占绝大多数活性，仅部分（75 - 90%）可被视黄酸抑制，而II型酶似乎即使有刺激也很微弱。因此，SCC细胞系似乎适合用于研究某些生理因子的生化作用机制、肿瘤细胞中分化功能调节改变的分子基础以及肿瘤内多样性的起源。
