Schwahn D J, Medina D
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Oncogene. 1998 Sep 3;17(9):1173-8. doi: 10.1038/sj.onc.1202038.
Differential display PCR [DD-PCR] was applied to identify mRNAs differentially expressed between two consecutive stages of an in vivo model of mouse mammary carcinogenesis. The extended life 12 [EL12] and transformed mammary 12 [TM12] outgrowths differ in morphology, ovarian hormone dependence, and tumorigenicity, yet the TM12 outgrowth arose spontaneously from the EL12 outgrowth. A fragment of the mouse p96 gene was identified using DD-PCR. The differential expression of p96 was confirmed using RNase protection assays. Examination of the RNA expression patterns of the p96 isoforms during normal mammary gland development showed high levels in the involuting mammary gland and in preneoplastic hyperplasias. In contrast, p96 isoform mRNA levels were consistently decreased in mammary tumors derived from the in vivo hyperplasias. Examination of p96 protein levels revealed a decrease in p96 protein in a number of mammary tumors as compared to their hyperplastic precursors further supporting the observations that p96 gene expression is consistently downregulated in mammary tumors. The functional activity of p96 protein has not been resolved, however the observation that p96 gene expression is downregulated in two different tumor systems (human ovarian tumors and mouse mammary tumors) warrants more extensive investigation on its role in normal and neoplastic cell growth.
差异显示PCR（DD-PCR）被用于鉴定小鼠乳腺癌发生体内模型两个连续阶段之间差异表达的mRNA。延长寿命12（EL12）和转化乳腺12（TM12）瘤块在形态、卵巢激素依赖性和致瘤性方面存在差异，但TM12瘤块是从EL12瘤块自发产生的。使用DD-PCR鉴定出小鼠p96基因的一个片段。使用核糖核酸酶保护分析证实了p96的差异表达。对正常乳腺发育过程中p96亚型的RNA表达模式进行检测，结果显示在退化期乳腺和肿瘤前增生组织中p96水平较高。相比之下，源自体内增生组织的乳腺肿瘤中p96亚型mRNA水平持续下降。对p96蛋白水平的检测显示，与增生性前体相比，许多乳腺肿瘤中p96蛋白减少，这进一步支持了p96基因表达在乳腺肿瘤中持续下调的观察结果。p96蛋白的功能活性尚未明确，但p96基因表达在两种不同肿瘤系统（人类卵巢肿瘤和小鼠乳腺肿瘤）中均下调这一观察结果，值得对其在正常和肿瘤细胞生长中的作用进行更广泛的研究。
