Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy.
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. DOI: http://dx.doi.org/10.7554/eLife.00996.001.
['Haricharan|Svasti|S|', 'Dong|Jie|J|', 'Hein|Sarah|S|', 'Reddy|Jay P|JP|', 'Du|Zhijun|Z|', 'Toneff|Michael|M|', 'Holloway|Kimberly|K|', 'Hilsenbeck|Susan G|SG|', 'Huang|Shixia|S|', 'Atkinson|Rachel|R|', 'Woodward|Wendy|W|', 'Jindal|Sonali|S|', 'Borges|Virginia F|VF|', 'Gutierrez|Carolina|C|', 'Zhang|Hong|H|', 'Schedin|Pepper J|PJ|', 'Osborne|C Kent|CK|', 'Tweardy|David J|DJ|', 'Li|Yi|Y|']
D000818:Animals D017209:Apoptosis D001943:Breast Neoplasms D063646:Carcinogenesis D002455:Cell Division D004195:Disease Models, Animal D005260:Female D051379:Mice D009154:Mutation D009857:Oncogenes D011247:Pregnancy D011252:Pregnancy Complications, Neoplastic D050799:STAT5 Transcription Factor
breast cancer pregnancy STAT5 chemoprevention