Department of Pathology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, He Xi District, China.
Am J Reprod Immunol. 2010 May;63(5):396-409. doi: 10.1111/j.1600-0897.2009.00807.x. Epub 2010 Feb 8.
Spontaneous breast cancer in Tientsin Albinao 2 (TA2) mice, like human pregnancy-associated breast cancer (PABC), often occurs in pregnancy and puerperium, especially in mice with high gravidity. We hypothesized that the dysfunction of cellular immunity caused by the increase of 17beta-estradiol (E2) and progesterone (P) might be one of the reasons for carcinogenesis of mammary gland.
We investigated the T lymphocyte subsets and the concentration of serum hormone and cytokines in cancer-bearing, pregnant or postpartum TA2 mice using flow cytometry, chemiluminescent immunoassay, and enzyme-linked immunosorbent assay (ELISA), respectively.
The number of T lymphocytes and the concentration of E2, P, interleukin-2 (IL-2), IL-4, and interferon-gamma (IFN-gamma) changed with the increase of pregnancy and puerperium. During four pregnancies, elevated E2 and P resulted in a decrease in the number of CD3(+), CD4(+) T lymphocytes, CD4(+)/CD8(+) ratio, and the concentration of IL-2, IL-4, and IFN-gamma. Data in the fourth pregnancy were the closest to those of cancer-bearing mice.
T lymphocyte subsets and concentration of IL-2, IL-4, and IFN-gamma are affected by E2 and P during multiple pregnancy and delivery to some degree, which may contribute to the genesis of spontaneous breast cancer in TA2 mice.
天津阿尔巴诺 2 号(TA2)小鼠的自发性乳腺癌与人类妊娠相关性乳腺癌(PABC)相似,常发生于妊娠和产褥期,尤其是高胎次的小鼠。我们推测,17β-雌二醇(E2)和孕酮(P)的增加导致细胞免疫功能障碍可能是乳腺发生癌变的原因之一。
我们采用流式细胞术、化学发光免疫分析和酶联免疫吸附试验(ELISA)分别检测荷瘤、妊娠或产后 TA2 小鼠 T 淋巴细胞亚群及血清激素和细胞因子的浓度。
随着妊娠和产褥期的增加,T 淋巴细胞数量以及 E2、P、白细胞介素-2(IL-2)、IL-4 和干扰素-γ(IFN-γ)的浓度发生变化。在四次妊娠期间,E2 和 P 的升高导致 CD3(+)、CD4(+)T 淋巴细胞数量、CD4(+)/CD8(+)比值以及 IL-2、IL-4 和 IFN-γ的浓度降低。第四次妊娠的数据与荷瘤小鼠最为接近。
E2 和 P 在多次妊娠和分娩过程中对 T 淋巴细胞亚群及 IL-2、IL-4 和 IFN-γ的浓度有一定影响,可能有助于 TA2 小鼠自发性乳腺癌的发生。