Calaf Gloria M
Center for Radiological Research, VC11-218, Columbia University Medical Center, New York, NY 10032, USA.
Int J Oncol. 2006 Feb;28(2):285-95.
Breast cancer is often hormone responsive with growth or regression of tumors modulated by endocrine manipulations. Estrogens are known to control the growth of many mammary carcinomas in experimental animals, and humans. Knowledge of tumor response to hormones will greatly improve the ability to plan therapy for breast cancer patients. Chemoprevention of breast cancer has been mostly aimed at reducing the rate of cell division through administration of anti-hormones. Tamoxifen has shown to be species, tissue, and cell-type specific. Cell proliferation in mammary gland occurs in a non-random fashion since there are specific compartments with varied rates of proliferation represented by the terminal end buds that are ready for differentiation into alveolar buds. The aim of this work was to study the effect of 17beta estradiol as well as an antiestrogen, tamoxifen in several in vitro systems to analyze the proliferative capabilities of different kind of cells under controlled experimental conditions. Normal, benign lesions, and duct carcinomas of human breast tissues were processed for organ culture. In the case of the normal breast tissue it was enzymatically digested and culture as organoid culture as well. Several immortalized normal and malignant human breast cell lines were also used in these studies to analyze the effect of 17beta estradiol, progesterone, tamoxifen and anti-progestin RU486. Both 17beta estradiol and progesterone stimulated cell proliferation whereas tamoxifen and RU486 inhibited such effect under these experimental conditions. Thus, in vitro systems allowed to analyze the proliferative capabilities of different kind of cells under controlled experimental conditions.
乳腺癌通常对激素有反应,肿瘤的生长或消退受内分泌操作调节。已知雌激素可控制实验动物和人类中许多乳腺癌的生长。了解肿瘤对激素的反应将大大提高为乳腺癌患者制定治疗方案的能力。乳腺癌的化学预防主要旨在通过给予抗激素来降低细胞分裂率。他莫昔芬已显示出具有物种、组织和细胞类型特异性。乳腺中的细胞增殖以非随机方式发生,因为存在特定的区域,其增殖速率各不相同,以准备分化为肺泡芽的终末芽为代表。这项工作的目的是研究17β-雌二醇以及抗雌激素他莫昔芬在几种体外系统中的作用,以分析在受控实验条件下不同类型细胞的增殖能力。对人乳腺组织的正常组织、良性病变和导管癌进行器官培养。对于正常乳腺组织,也将其酶消化并作为类器官培养物进行培养。在这些研究中还使用了几种永生化的正常和恶性人乳腺细胞系,以分析17β-雌二醇、孕酮、他莫昔芬和抗孕激素RU486的作用。在这些实验条件下,17β-雌二醇和孕酮均刺激细胞增殖,而他莫昔芬和RU486则抑制这种作用。因此,体外系统能够在受控实验条件下分析不同类型细胞的增殖能力。