TY - JOUR T1 - The Hedgehog Signaling Pathway Plays an Essential Role in Maintaining the CD44<sup>+</sup>CD24<sup>-/low</sup> Subpopulation and the Side Population of Breast Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 2147 LP - 2157 VL - 29 IS - 6 AU - HARUO TANAKA AU - MASAFUMI NAKAMURA AU - CHIZU KAMEDA AU - MAKOTO KUBO AU - NORIHIRO SATO AU - SYOJI KUROKI AU - MASAO TANAKA AU - MITSUO KATANO Y1 - 2009/06/01 UR - http://ar.iiarjournals.org/content/29/6/2147.abstract N2 - The side population (SP) and the CD44+/CD24-/low population have been reported in separate studies to include more tumorigenic cells than other populations, and to have the ability to form new tumors and undergo heterogeneous differentiation in breast cancer tissue. However, the relationship between these two populations has not yet been explored in breast cancer cells. Here it is shown that the SP and the CD44+/CD24-/low populations are overlapping. Both populations were resistant to paclitaxel. Components of the Hedgehog (Hh) signaling pathway were more highly expressed in these cell populations at both the mRNA and protein levels compared with other populations. Furthermore, inhibition of Hh signaling activity suppressed the proliferation of both populations. The significance of Hh signaling activity in the proliferation of both populations was confirmed by the effect of an si-RNA against Gli1, a trans-activator of the Hh signaling pathway, on the proliferation of both populations. These data suggest that the Hh signaling pathway is essential for the proliferation of the tumorigenic population of breast cancer cells, and that this pathway might represent a new candidate for breast cancer therapy targeting cancer stem cells. ER -