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低肿瘤发生率和高肿瘤发生率小鼠品系中化学致癌物诱导的乳腺肿瘤中的小鼠乳腺肿瘤病毒基因组表达

Mouse mammary tumor virus genome expression in chemical carcinogen-induced mammary tumors in low- and high-tumor-incidence mouse strains.

作者信息

Dusing-Swartz S, Medina D, Butel J S, Socher S H

出版信息

Proc Natl Acad Sci U S A. 1979 Oct;76(10):5360-4. doi: 10.1073/pnas.76.10.5360.

DOI:10.1073/pnas.76.10.5360
PMID:228289
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC413142/
Abstract

Involvement of mouse mammary tumor virus (MMTV) in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis was investigated in low- (BALB/c) and high- (BALB/cfC3H) mammary-tumor-incidence mouse strains. Both strains contain endogenous MMTV integrated into the cellular genome. Additionally, BALB/cfC3H mice are infected with exogenous MMTV-S which is responsible for a higher incidence of mammary tumors in breeding females. Administration of DMBA to virgin mice of both strains resulted in a moderate frequency of mammary tumors within 40 wk after treatment. No differences were found in DMBA-induced tumor incidences at 18 wk (6% and 7%) or at 38 wk (29% and 36%) after treatment of BALB/c and BALB/cfC3H mice, respectively. Expression of MMTV in these tumors was examined by assaying for the presence of MMTV RNA by hybridization using MMTV-specific cDNA and by immunohistochemical staining utilizing antibodies against MMTV 52,000-dalton glycoprotein, gp52, and 28,000-dalton internal protein, p28. Of 16 BALB/c tumors assayed, 11 did not contain detectable levels of MMTV RNA and the remaining 5 tumors contained only low levels (0.0005-0.0010%) of viral RNA. Importantly, MMTV RNA was not detected in 5 of 27 BALB/cfC3H tumors. The other BALB/cfC3H tumors contained quantities of MMTV RNA ranging from 0.0006 to 0.4170%. Most BALB/cfC3H tumors with detectable levels of MMTV RNA also synthesized viral proteins gp52 and p28. Thus, expression of the complete MMTV genome is not requisite for maintenance of the tumor phenotype in DMBA-induced mammary tumors in either BALB/c or BALB/cfC3H virgin mice under 1 year of age.

摘要

在低乳腺肿瘤发病率的(BALB/c)和高乳腺肿瘤发病率的(BALB/cfC3H)小鼠品系中,研究了小鼠乳腺肿瘤病毒(MMTV)在7,12-二甲基苯并[a]蒽(DMBA)诱导的乳腺肿瘤发生中的作用。这两个品系都含有整合到细胞基因组中的内源性MMTV。此外,BALB/cfC3H小鼠感染了外源性MMTV-S,这导致繁殖雌性小鼠乳腺肿瘤的发病率更高。对两个品系的处女小鼠给予DMBA后,在治疗后40周内乳腺肿瘤的发生频率适中。分别对BALB/c和BALB/cfC3H小鼠进行治疗后,在18周(6%和7%)或38周(29%和36%)时,DMBA诱导的肿瘤发生率没有差异。通过使用MMTV特异性cDNA杂交检测MMTV RNA的存在,以及利用针对MMTV 52,000道尔顿糖蛋白gp52和28,000道尔顿内部蛋白p28的抗体进行免疫组织化学染色,来检测这些肿瘤中MMTV的表达。在检测的16个BALB/c肿瘤中,11个未检测到可检测水平的MMTV RNA,其余5个肿瘤仅含有低水平(0.0005 - 0.0010%)的病毒RNA。重要的是,在27个BALB/cfC3H肿瘤中的5个中未检测到MMTV RNA。其他BALB/cfC3H肿瘤中MMTV RNA的含量范围为0.0006%至0.4170%。大多数检测到MMTV RNA的BALB/cfC3H肿瘤也合成病毒蛋白gp52和p28。因此,在1岁以下的BALB/c或BALB/cfC3H处女小鼠中,DMBA诱导的乳腺肿瘤中,完整MMTV基因组的表达对于维持肿瘤表型不是必需的。

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