Allele-specific patterns of the mouse parathyroid hormone-related protein: Influences on cell adhesion and migration

Research output: Contribution to journalArticlepeer-review

Abstract

The mouse parathyroid hormone-like hormone PthlhPro and PthlhThr variants are linked with susceptibility and resistance to skin carcinogenesis of Car-S and Car-R mice, respectively, and with in vitro effects (Oncogene, 19: 5324-5328, 2000). We have identified an additional Pthlh variant, consisting of Thr and three amino-acid changes in the C-terminus (PthlhSerAspTyr), carried by an evolutionarily distant Mus spretus (SPRET/Ei) inbred strain. When transfected into NCI-H520 tumor cells, this PthlhSerAspTyr variant did not stimulate tumor growth in nude mice. Analysis of cell adhesion, migration, and invasion patterns of Pthlh Pro-, PthlhThr-, and PthlhSerAspTyr- transfected NCI-H520 cells revealed a 1.5-fold decrease in adhesion efficiency on both collagen type I and Matrigel, and a 5-6-fold increase in migration capability in Pthlhpro transfectants as compared to nontransfected, vector-transfected, PthlhThr-, or PthlhSerAspTyr- transfected cells. These findings suggest that the cancer modifier effects of the mouse Pthlh gene are mediated by differential cell adhesion and migration effects of PTHrP variants.

Original languageEnglish
Pages (from-to)7711-7715
Number of pages5
JournalOncogene
Volume22
Issue number49
DOIs
Publication statusPublished - Oct 30 2003

Keywords

  • Cancer modifier genes
  • Genetic susceptibility
  • Polymorphism skin cancer

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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