Jamerson M Hunter, Johnson Michael D, Furth Priscilla A, Dickson Robert B
Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road, NW, Washington, DC 20057, USA.
Transgenic Res. 2003 Dec;12(6):747-50. doi: 10.1023/b:trag.0000005247.69329.ca.
Female transgenic mice, in which a murine c-myc gene has been placed under the transcriptional control of the mouse mammary tumor virus long terminal repeat, are prone to developing mammary adenocarcinomas. Owing to the manner in which these mammary tumors develop, it is clear that exogenous expression of the c-myc transgene is necessary to but insufficient for murine mammary tumorigenesis. The genetic background of study mice has been shown to influence the phenotype induced by different transgenes; furthermore, mammary tumor initiation and progression induced by different transgenes has been shown to be susceptible to significant modification with alterations in and mixing of the genetic background of the study mice. We bred MMTV-c-myc transgenic mice onto a mixed genetic background that resulted in a very significant suppression of mammary tumor incidence for parous mice, bred continuously starting at 10 weeks of age. In this paper, we show that mammary tumor incidence is significantly elevated in these mixed background MMTV-c-myc transgenic mice when they are bred continuously, starting at 7 weeks of age. Early breeding of these mice did not influence mammary tumor multiplicity, latency, histopathology, or number of pregnancies at time of tumor development. These results are the first to demonstrate that breeding age influences mammary tumor incidence in MMTV-c-myc transgenic mice. They suggest that mammary gland susceptibility to tumorigenesis, resulting from the expression of c-myc, may vary with glandular development as is seen for chemical carcinogens.
雌性转基因小鼠，其鼠源c-myc基因已置于小鼠乳腺肿瘤病毒长末端重复序列的转录控制之下，易于发生乳腺腺癌。由于这些乳腺肿瘤的发展方式，很明显c-myc转基因的外源表达对于鼠类乳腺肿瘤发生是必要的，但并不充分。已表明研究小鼠的遗传背景会影响不同转基因诱导的表型；此外，已表明不同转基因诱导的乳腺肿瘤起始和进展会因研究小鼠遗传背景的改变和混合而受到显著修饰。我们将MMTV-c-myc转基因小鼠培育到混合遗传背景上，这导致对从10周龄开始连续繁殖的经产小鼠的乳腺肿瘤发生率有非常显著的抑制。在本文中，我们表明，当这些混合背景的MMTV-c-myc转基因小鼠从7周龄开始连续繁殖时，其乳腺肿瘤发生率会显著升高。这些小鼠的早期繁殖并不影响乳腺肿瘤的多样性、潜伏期、组织病理学或肿瘤发生时的妊娠次数。这些结果首次证明繁殖年龄会影响MMTV-c-myc转基因小鼠的乳腺肿瘤发生率。它们表明，由c-myc表达导致的乳腺对肿瘤发生的易感性可能会随着腺体发育而变化，就像化学致癌物的情况一样。
