Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy
Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy
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作者：
Haricharan, Svasti;Dong, Jie;Li, Yi
虽然22岁之前的第一次怀孕降低了乳腺癌的风险，但35岁之后的怀孕显著增加了终身乳腺癌的风险。怀孕会导致正常乳房的几个变化，增加了转化的障碍，但怀孕如何也会增加癌症风险仍不清楚。我们在小鼠身上表明，怀孕对正常乳腺中已经发展起来的少数早期病变有不同的影响--它导致细胞凋亡逃避和加速癌变。这些癌前细胞在妊娠/哺乳激素的作用下激活STAT5，即使在退化期也保持STAT5的激活，从而阻止通常由癌蛋白和退化期启动的细胞凋亡。对哺乳期完成的早期病变的小鼠进行短期抗STAT5治疗，可以消除怀孕后增加的风险。这一化学预防策略对预防因怀孕而增加的人类乳腺癌风险具有重要意义。
While a first pregnancy before age 22 lowers breast cancer risk, a pregnancy after age 35 significantly increases life-long breast cancer risk. Pregnancy causes several changes to the normal breast that raise barriers to transformation, but how pregnancy can also increase cancer risk remains unclear. We show in mice that pregnancy has different effects on the few early lesions that have already developed in the otherwise normal breast-it causes apoptosis evasion and accelerated progression to cancer. The apoptosis evasion is due to the normally tightly controlled STAT5 signaling going astray-these precancerous cells activate STAT5 in response to pregnancy/ lactation hormones and maintain STAT5 activation even during involution, thus preventing the apoptosis normally initiated by oncoprotein and involution. Short-term anti-STAT5 treatment of lactation-completed mice bearing early lesions eliminates the increased risk after a pregnancy. This chemoprevention strategy has important implications for preventing increased human breast cancer risk caused by pregnancy.