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.

journal_name

Cancer Res

journal_title

Cancer research

authors

Lee Y,Miller HL,Russell HR,Boyd K,Curran T,McKinnon PJ

doi

10.1158/0008-5472.CAN-06-0505

subject

Has Abstract

pub_date

2006-07-15 00:00:00

pages

6964-71

issue

14

eissn

0008-5472

issn

1538-7445

pii

66/14/6964

journal_volume

66

pub_type

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