Progression of Hormone-Dependent Mammary Tumors After Dormancy: Role of Wnt Pathway

摘要: The cancer stem cell theory suggests the existence of cells within breast cancers that possess ability to self-renew and differentiate, albeit in a deregulated manner, which sustains tumor progression. Therefore, latent tumors and/or their metastasis may eventually resume growth thorough signals impacting on niche. Since it has been determined Wingless Related Protein (Wnt) signaling is likely niche factor regulator Mammary Stem Cells dynamics, conceivable this pathway play significant role “awakening” dormant tumors. We have previously shown virgin females, MMTV-induced pregnancy-dependent (ER+PR+) transplants were able remain for up 300 days, but after hormone stimulation. In subsequent transplant generation, all these became ER−PR− grew indicating dormancy facilitated progression hormone-independence. Our data also showed mutations altering expression genes involved Wnt prone be selected during To gain more insight into mechanisms underlying observations, we compared gene profile either underwent or not before progressing hormone-independency. Confirming our reported data, found most up-regulated hormone-independent progressed was Wnt1. addition, group systematic down-modulation described mediators normal pubertal mammary gland development. Using hierarchical clustering analysis classify patients, identified specific carcinomas with modulation resumed dormancy. Interestingly, human samples mainly composed by patients basal-like carcinomas, down-regulation associated believe cluster co-regulated basal mouse resuming might mechanistically activation pathway, induce proliferation from progenitor cells.