Obesity-mediated regulation of HGF/c-Met is associated with reduced basal-like breast cancer latency in parous mice
Sundaram S, Freemerman AJ, Galanko JA, McNaughton KK, Bendt KM, Darr DB, Troester MA, Makowski, L.
PLoS ONE 9(10): e111394. doi:10.1371/journal.pone.0111394
Lay Abstract
Basal-like breast cancers (BBCs) lack estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) protein expression, thus are often referred to as “triple-negative” breast cancers, and as such these cancers lack a targeted therapy. In population studies, a full term pregnancy (parity) reduces the risk for estrogen receptor positive (ER+) breast cancers, while parity is associated with increased risk of BBC subtype – but mechanisms remain unknown. Experimental studies have examined parity and obesity individually, but the joint effects of parity and obesity had not been studied. Therefore we investigated the role of obesity in parous mice on BBC. We found that parity alone dramatically decreased time to tumor compared to nulliparous controls – in other words, tumors came on more sooner. Obesity had only a minor role in further reducing time to tumor in parous mice relative to nulliparity. In the normal mammary glands of parous mice, we discovered that c-Met concentrations were 2.5-fold greater with obesity, suggesting a role for the c-Met cancer-driving pathway in BBC risk with pregnancy. It is unclear if pregnancy and obesity in humans drive activation of the same pathway. The best news is that breastfeeding helps reduce risk of BBC, thus maintaining a healthy weight and breastfeeding are important actions to help reduce risk of this aggressive cancer. |
