Purpose: Breast cancer is caused by rare populations of self-renewing cancer stem cells that might also play a role in tumor relapse. Genes that regulate cancer stem cells are, therefore, of great interest in controlling cancer. EZH2 gene expression is reported to be elevated during breast cancer progression and it plays a role in expanding breast stem cell populations. In the current study, we analyzed the correlation between the silencing effect of EZH2 and breast cancer stem cell expansion.
Methods: We used CD44+/CD24-/low cells to develop initial-, moderate-, and advanced-stage breast cancers in female NOD/SCID mice. Immunohistochemistry and western blotting were used to study the expression of aldehyde dehydrogenase 1 (ALDH1) and EZH2 in different stages of breast cancer.
Results: Histology showed that as tumors progressed, the pathological condition changed exhibiting enlarged nuclei, higher cell proliferation, and more invasive cells. In EZH2-silenced mice histopathology also showed enlarged cell nucleus, lesion formation and cell aggregation. Immunohistochemistry and western blotting analyses of EZH2 and ALDH1 demonstrated elevated expression as tumors progressed to the next level. Interestingly, the expression of ALDH1 in EZH2-silenced breast cancer tissue showed prolonged overexpression.
Conclusions: We conclude that the normal expression of EZH2 in cancer tissue controls cancer stem cell expansion, because it is highly elevated in EZH2-silencing cancer tissue.