Santarelli R, Tzeng Y J, Zimmermann C, Guhl E, Graessmann A
Institut für Molekularbiologie und Biochemie, Freien Universität Berlin, Germany.
Oncogene. 1996 Feb 1;12(3):495-505.
The whey acid protein (WAP) is a major mouse milk protein and its gene expression is induced by various lactotrophic hormones (eg, estrogen, progesterone). Transgenic animals harboring the early SV40 coding region (T/t-antigen) under the transcriptional control of the WAP promoter develop breast cancer after the first lactation period. The tumor cells synthesize the SV40 T-antigen with a high efficiency indicating that WAP-SV-T expression escapes down-regulation after the lactation period. However about 5-10% of the tumors became T-antigen negative during tumor progression and WAP-SV-T expression was only demonstrable by PCR analysis. Both T-antigen positive and negative tumor cells expressed the estrogen and progesterone receptor at a comparable rate, indicating that hormone receptor levels do not determine expression of the WAP-SV-T transgene. Furthermore, WAP and WAP-SV-T gene expression are not restricted to the pregnancy-lactation period. Virgin animals also express both genes with a low efficiency and about 70% of these animals also developed T-antigen positive breast tumors. The tumor rate however was strongly reduced in ovariectomized animals, indicating that the ovary hormones play a critical role in breast cancer formation.
乳清酸蛋白（WAP）是小鼠乳汁中的一种主要蛋白质，其基因表达受多种促乳激素（如雌激素、孕酮）诱导。在WAP启动子转录控制下携带早期SV40编码区（T/t抗原）的转基因动物在首次哺乳期后会发生乳腺癌。肿瘤细胞高效合成SV40 T抗原，这表明哺乳期后WAP-SV-T表达逃避了下调。然而，在肿瘤进展过程中约5-10%的肿瘤变为T抗原阴性，且WAP-SV-T表达仅通过PCR分析得以证实。T抗原阳性和阴性肿瘤细胞以相当的比率表达雌激素和孕酮受体，这表明激素受体水平并不决定WAP-SV-T转基因的表达。此外，WAP和WAP-SV-T基因表达并不局限于妊娠-哺乳期。未生育动物也低效表达这两种基因，且这些动物中约70%也发生了T抗原阳性乳腺肿瘤。然而，去卵巢动物的肿瘤发生率显著降低，这表明卵巢激素在乳腺癌形成中起关键作用。
