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.
Molecular Biology Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Roberto
R
Benelli
Bernard
B
Peissel
Giacomo
G
Manenti
Manuela
M
Gariboldi
Christian
C
Vanzetto
Adriana
A
Albini
Tommaso A
TA
Dragani
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