Dicker A J, Serewko M M, Dahler A L, Khanna K K, Kaur P, Li A, Strutton G M, Saunders N A
Epithelial Pathobiology Group, University of Queensland Department of Medicine, Brisbane, Queensland, Australia.
Exp Cell Res. 2000 Aug 1;258(2):352-60. doi: 10.1006/excr.2000.4944.
We have successfully isolated a cell line (IEC-1) from an intraepidermal carcinoma of the skin of a patient and compared its behavior, in vitro, to normal human epidermal keratinocytes (HEK) and squamous cell carcinoma cell lines (SCCs). HEK differentiation comprises an initial growth arrest followed by an induction of squamous differentiation-specific genes such as transglutaminase type 1 (TG-1). Using thymidine uptake and TG-1 induction as markers of proliferation and differentiation, respectively, we were able to show that HEKs and the IEC-1 cells undergo growth arrest and induce TG-1 mRNA expression in response to various differentiation-inducing stimuli, while neoplastic SCC cell lines did not. However, differentiation in HEKs was an irreversible process whereas differentiation of the IEC-1 cells was reversible. Furthermore, growth of IEC-1 cells in organotypic raft cultures revealed differences in their ability to complete a squamous differentiation program compared with that of normal HEKs. The IEC-1 cells also exhibited a transitional phenotype with respect to replicative lifespan; HEKs had a lifespan of 4-6 passages, IEC-1 cells of 15-17 passages, and SCC cells were immortal. These alterations in IEC-1 cell behavior were not associated with functional inactivation or mutations of the p53 gene. These data indicate that the IEC-1 cells, derived from a preneoplastic skin tumor, exhibit differences in their ability to undergo terminal differentiation and have an extended replicative lifespan.
我们成功地从一名患者皮肤的表皮内癌中分离出一种细胞系（IEC-1），并在体外将其行为与正常人表皮角质形成细胞（HEK）和鳞状细胞癌细胞系（SCC）进行了比较。HEK分化包括最初的生长停滞，随后诱导鳞状分化特异性基因，如1型转谷氨酰胺酶（TG-1）。分别使用胸苷摄取和TG-1诱导作为增殖和分化的标志物，我们能够表明，HEK和IEC-1细胞在受到各种分化诱导刺激时会经历生长停滞并诱导TG-1 mRNA表达，而肿瘤性SCC细胞系则不会。然而，HEK中的分化是一个不可逆的过程，而IEC-1细胞的分化是可逆的。此外，与正常HEK相比，IEC-1细胞在器官型筏式培养中的生长显示出它们完成鳞状分化程序的能力存在差异。IEC-1细胞在复制寿命方面也表现出过渡表型；HEK的寿命为4 - 6代，IEC-1细胞为15 - 17代，SCC细胞是永生的。IEC-1细胞行为的这些改变与p53基因的功能失活或突变无关。这些数据表明，源自癌前皮肤肿瘤的IEC-1细胞在经历终末分化的能力方面存在差异，并且具有延长的复制寿命。
