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

被引：8
作者：
Benelli, R
Peissel, B
Manenti, G
Gariboldi, M
Vanzetto, C
Albini, A
Dragani, TA
机构：
[1] Ist Nazl Tumori, Dept Expt Oncol, I-20133 Milan, Italy
[2] Ist Nazl Ric Canc, Mol Biol Lab, I-16132 Genoa, Italy
来源：
ONCOGENE | 2003年 / 22卷 / 49期
关键词：
cancer modifier genes; genetic susceptibility; polymorphism skin cancer;
D O I：
10.1038/sj.onc.1207088
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The mouse parathyroid hormone-like hormone Pthlh(Pro) and Pthlh(Thr) 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 (Pthlh(SerAspTyr)), carried by an evolutionarily distant Mus spretus (SPRET/Ei) inbred strain. When transfected into NCI-H520 tumor cells, this Pthlh(SerAspTyr) variant did not stimulate tumor growth in nude mice. Analysis of cell adhesion, migration, and invasion patterns of Pthlh(Pro)-, Pthlh(Thr)-, and Pthlh(SerAspTyr)- 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 Pthlh(Pro) transfectants as compared to nontransfected, vector-transfected, Pthlh(Thr)-, or Pthlh(SerAspTyr)- 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.
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页码：7711 / 7715
页数：5
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