Abstract 4214: Stem cell antigen-1 (Sca1) modulates PI3K/PTEN signaling and mammary tumor cell survival

Stem cell antigen-1 (Sca-1, Ly6A/E) represents two allelic forms of a GPI-anchored membrane protein that was first identified as a murine marker of bone marrow stem cells. Although Sca-1 is widely used to enrich for stem cells in many normal tissues, little is known about its function and associated signaling pathways in tumorigenesis. To explore this further, mammary carcinogenesis was induced in Sca-1+/EGFP mice that are heterozygous for Sca-1 and express GFP under the control of the Sca-1 locus. Induction of mammary tumorigenesis by progestin/DMBA treatment resulted in a marked increase of Sca-1 in the mammary gland at the initiation of tumorigenesis, as well as in the resulting tumors. To further investigate the function of Sca1, tumor cell line 34T was established from a primary adenocarcinoma, and sorted into Sca-1hi and Sca-1lo populations. These results revealed that Sca-1 expression related inversely with proliferation, as well as PTEN, PDK1, pT308Akt and pERK1/2 expression. Furthermore, reduction of Sca-1 in 34T cells by lentivirus-mediated RNAi reversed the proliferative, PTEN and kinase phenotype, and resulted in loss of their ability to proliferate as spheroid clusters in cell culture. Isografts of 34T/Sca-1hi and 34T/Sca-1lo cells in syngeneic mice indicated that Sca-1 was essential for tumorigenicity. These results provide evidence that Sca-1 confers a proliferative and survival advantage to mammary tumor cells, and demonstrates for the first time that Sca1 is associated with modulation of the PTEN/PDK1/Akt axis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4214.