Simian Marina, Manzur Teresita, Rodriguez Vanina, de Kier Joffé Elisa Bal, Klein Slobodanka
Research Area, Institute of Oncology Angel H. Roffo, University of Buenos Aires, Av. San Martín 5481, (C1417DTB), Buenos Aires, Argentina.
Breast Cancer Res Treat. 2009 Jan;113(1):1-8. doi: 10.1007/s10549-007-9888-x. Epub 2008 Jan 9.
Currently, an in vivo spontaneous model of estrogen dependent, tamoxifen sensitive breast cancer does not exist. We show here the characterization of the M05 mammary tumor that appeared spontaneously in a 1-year-old virgin female BALB/c mouse in our animal facility. The M05 tumor is a semi-differentiated adenocarcinoma that expresses estrogen and progesterone receptors. When it was transplanted to either male or ovariectomized female mice it did not grow. Moreover, ovariectomy or treatment with tamoxifen of tumor bearing mice led to a halt in tumor growth. Treatment of ovariectomized mice that had been inoculated with the M05 tumor showed that only estradiol, but not progesterone, promoted the re-growth of the tumor. Finally, after passage nine, tumor growth was achieved in male and ovariectomized female mice suggesting that the tumor had progressed to hormone independence. However, like often found in the clinic, expression of estrogen and progesterone receptors was maintained. This model mimics the biology of estrogen receptor positive breast cancer in humans and presents itself as an invaluable tool for the study of endocrine resistance in a physiologically relevant setting.
目前,尚无雌激素依赖性、对他莫昔芬敏感的乳腺癌体内自发模型。我们在此展示了在我们动物设施中一只1岁处女雌性BALB/c小鼠体内自发出现的M05乳腺肿瘤的特征。M05肿瘤是一种半分化腺癌,表达雌激素和孕激素受体。当将其移植到雄性或去卵巢雌性小鼠体内时,肿瘤不会生长。此外,对荷瘤小鼠进行卵巢切除或用他莫昔芬治疗会导致肿瘤生长停止。对接种了M05肿瘤的去卵巢小鼠的治疗表明,只有雌二醇而非孕激素能促进肿瘤重新生长。最后,传代九次后,雄性和去卵巢雌性小鼠中实现了肿瘤生长,这表明肿瘤已发展为激素非依赖性。然而,如同在临床上经常发现的那样,雌激素和孕激素受体的表达得以维持。该模型模拟了人类雌激素受体阳性乳腺癌的生物学特性,是在生理相关环境中研究内分泌抵抗的宝贵工具。