Rasmussen U B, Wolf C, Mattei M G, Chenard M P, Bellocq J P, Chambon P, Rio M C, Basset P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, INSERM-Institut de Chimie Biologique-Faculté de Médecine, Strasbourg, France.
Cancer Res. 1993 Sep 1;53(17):4096-101.
A new complementary DNA, p27, has been cloned and sequenced from estradiol-treated MCF7 human breast carcinoma cells. It encodes a putative highly hydrophobic protein of 122 amino acids which has a 33% overall sequence similarity to the product of the 6-16 gene (R. L. Friedman, S. P. Manly, M. McMahon, I. M. Kerr, and G. R. Stark, Cell, 38: 745-755, 1984), which is transcriptionally induced by interferons of the alpha/beta type. We demonstrate here that the p27 gene, which is located in band q32 of human chromosome 14, is also induced by interferon-alpha in human cell lines of different origin and that expression is independent of the presence of estradiol receptor in the cells. High levels of p27 RNA were found in vivo in approximately 50% of primary human breast carcinomas (21 were tested by Northern blotting). In situ hybridization to some of the p27-overexpressing tumors showed that the p27 RNA is localized in cancer cells and sometimes also in fibroblastic cells of tumor stroma. p27 RNA levels in the tumors did not correlate with the presence of estrogen receptor or with the expression of the estrogen-induced pS2 gene. Further studies are now necessary to elucidate the cause of p27 gene overexpression in breast carcinoma and in particular to determine whether it corresponds to chromosomal rearrangements in the 14q32 region and/or to induction by interferons of the alpha/beta type.
从经雌二醇处理的MCF7人乳腺癌细胞中克隆并测序了一种新的互补DNA，即p27。它编码一种推测的由122个氨基酸组成的高度疏水蛋白，该蛋白与6 - 16基因（R. L. 弗里德曼、S. P. 曼利、M. 麦克马洪、I. M. 克尔和G. R. 斯塔克，《细胞》，38: 745 - 755，1984年）的产物在整体序列上有33%的相似性，6 - 16基因可被α/β型干扰素转录诱导。我们在此证明，位于人类染色体14 q32带的p27基因，在不同来源的人类细胞系中也可被α干扰素诱导，且其表达与细胞中雌激素受体的存在无关。在大约50%的原发性人类乳腺癌中发现了体内高水平的p27 RNA（通过Northern印迹法检测了21例）。对一些p27过表达肿瘤的原位杂交显示，p27 RNA定位于癌细胞，有时也定位于肿瘤基质的成纤维细胞中。肿瘤中的p27 RNA水平与雌激素受体的存在或雌激素诱导的pS2基因的表达无关。现在需要进一步研究来阐明乳腺癌中p27基因过表达的原因，特别是要确定它是否对应于14q32区域的染色体重排和/或α/β型干扰素的诱导。
