Induction of a Pregnancy-Like Mammary Gland Differentiation by Docosapentaenoic Omega-3 Fatty Acid

The protective effect of early pregnancy against breast cancer can be attributed to the transition from undifferentiated cells in the nulliparous to the differentiated mature cells during pregnancy. Considerable evidences suggest strongly that the n-3 polyunsaturated fatty acid PUFA content of adipose breast tissue is inversely associated with an increased risk of breast cancer. Here we report that there was a decrease in n-6n-3 PUFA ratio and a significant increase in concentration of n-3 PUFA DPA and EPA in the pregnant gland. The functional role of n-3 PUFAs on differentiation was supported by the studies in fat-1 transgenic mouse, which converts endogenous n- 6 to n-3 PUFAs. Thus, alternation of n-6n-3 fatty acid compositional ratio in favor of n-3 PUFA and particularly DPA and EPA is one of the underlying mechanisms of pregnancy-induced mammary differentiation. DPA induced mammary gland functional differentiation is dependent on Jak2-Stat5 signaling. Treatment of experimental animals with DPA reduces carcinogen-induced mammary tumorigenesis.