title: Patched2 modulates tumorigenesis in patched1 heterozygous mice.
abstract: The sonic hedgehog (SHH) receptor Patched 1 (Ptch1) is critical for embryonic development, and its loss is linked to tumorigenesis. Germ line inactivation of one copy of Ptch1 predisposes to basal cell carcinoma and medulloblastoma in mouse and man. In many cases, medulloblastoma arising from perturbations of Ptch1 function leads to a concomitant up-regulation of a highly similar gene, Patched2 (Ptch2). As increased expression of Ptch2 is associated with medulloblastoma and other tumors, we investigated the role of Ptch2 in tumor suppression by generating Ptch2-deficient mice. In striking contrast to Ptch1-/- mice, Ptch2-/- animals were born alive and showed no obvious defects and were not cancer prone. However, loss of Ptch2 markedly affected tumor formation in combination with Ptch1 haploinsufficiency. Ptch1+/-Ptch2-/- and Ptch1+/-Ptch2+/- animals showed a higher incidence of tumors and a broader spectrum of tumor types compared with Ptch1+/- animals. Therefore, Ptch2 modulates tumorigenesis associated with Ptch1 haploinsufficiency.
authors.affiliation: Department of Genetics, St Jude Children's Research Hospital, Memphis, Tennessee. 38105, USA
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Lee
authors.forename: Heather L
authors.initials: HL
authors.lastname: Miller
authors.forename: Helen R
authors.initials: HR
authors.lastname: Russell
authors.forename: Kelli
authors.initials: K
authors.lastname: Boyd
authors.forename: Tom
authors.initials: T
authors.lastname: Curran
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McKinnon
mesh_terms: D000483:Alleles; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D008297:Male; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism
chemical_list: D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; C000606240:Ptch1 protein, mouse; C000606241:Ptch2 protein, mouse; D011956:Receptors, Cell Surface