Allele-specific patterns of the mouse parathyroid hormone-related protein: influences on cell adhesion and migration.
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.
Benelli
Roberto
R
Molecular Biology Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Peissel
Bernard
B
Manenti
Giacomo
G
Gariboldi
Manuela
M
Vanzetto
Christian
C
Albini
Adriana
A
Dragani
Tommaso A
TA
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002465:Cell Movement; D020022:Genetic Predisposition to Disease; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009115:Muridae; D041681:NIH 3T3 Cells; D044162:Parathyroid Hormone-Related Protein / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011110:Polymorphism, Genetic; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014162:Transfection
D044162:Parathyroid Hormone-Related Protein