title: NEROFE--a novel human hormone-peptide with anti-cancer activity.
abstract: We report the isolation of a novel Tumor-Cells Apoptosis Factor (Nerofe). We found that cDNA of this protein is expressed mainly in the human thymus and partially in the colon and in the frontal lobe of brain. Immunohistochemical studies localize Tumor-Cells Apoptosis Factor (TCApF) to the medulla and Hassal's corpuscles of the thymus gland, which are responsible for negative selection. Treatment of mice with induced AML terminates the cancer development and completely eliminates metastatic cell colonies from the bone marrow and the spleen that reduces probability of the cancer return. We find that TCApF binds to the T1/ST2 receptor and activates caspases 8, 9 and 3 mediated apoptosis, together with activation of JNKinase and p38 MAPKinase. Application of TCApF to cells induced apoptosis in acute myeloid leukemia proliferating cells (U937 premeyloid cells), in human breast carcinoma (MCF7), human glioblastoma, human neuroblastoma, human prostate cancer and human lung cancer proliferating cells. In contrast, TCApF was unable to induce apoptosis in non-proliferating cells. The selectivity of TCApF-induced apoptosis is related to the level of T1/ST2 receptor expression. This is the first report linking the T1/ST2 receptor to apoptosis.
authors.affiliation: Department of Computational Chemistry, Jerusalem College of Technology, Jerusalem, Israel. sandler@jct.ac.il
authors.forename: Uziel
authors.initials: U
authors.lastname: Sandler
authors.forename: Orly
authors.initials: O
authors.lastname: Devary
authors.forename: Ori
authors.initials: O
authors.lastname: Braitbard
authors.forename: Joel
authors.initials: J
authors.lastname: Ohana
authors.forename: Gideon
authors.initials: G
authors.lastname: Kass
authors.forename: Ariel M
authors.initials: AM
authors.lastname: Rubinstein
authors.forename: Zeev Y
authors.initials: ZY
authors.lastname: Friedman
authors.forename: Yoram
authors.initials: Y
authors.lastname: Devary
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D011956:Receptors, Cell Surface / Q000378:metabolism; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010455:Peptides; D011956:Receptors, Cell Surface; C555442:tumor-cells apoptosis factor, human