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.

引用

页码：7711 / 7715

页数：5

共 23 条

[1] Parathyroid hormone-related peptide is a potent tumor angiogenic factor
Akino, K
Ohtsuru, A
Kanda, K
Yasuda, A
Yamamoto, T
Akino, Y
Naito, S
Kurokawa, M
Iwahori, N
Yamashita, S
[J]. ENDOCRINOLOGY, 2000, 141 (11) : 4313 - 4316
[2] ALBINI A, 1987, CANCER RES, V47, P3239
[3] Albini A, 1998, Pathol Oncol Res, V4, P230
[4] Parathyroid hormone-related peptide is a naturally occurring, protein kinase A-dependent angiogenesis inhibitor
Bakre, MM
Zhu, YH
Yin, H
Burton, DW
Terkeltaub, R
Deftos, LJ
Varner, JA
[J]. NATURE MEDICINE, 2002, 8 (09) : 995 - 1003
[5] Boccellino M, 2000, J CELL PHYSIOL, V183, P254, DOI 10.1002/(SICI)1097-4652(200005)183:2<254::AID-JCP12>3.0.CO
[6] 2-U
[7] Cell adhesion in tumor invasion and metastasis: loss of the glue is not enough
Cavallaro, U
Christofori, G
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2001, 1552 (01): : 39 - 45
[8] The COOH-terminus of parathyroid hormone-related protein (PTHrP) interacts with β-arrestin 1B
Conlan, LA
Martin, TJ
Gillespie, MT
[J]. FEBS LETTERS, 2002, 527 (1-3) : 71 - 75
[9] The C-terminal region of PTHrP, in addition to the nuclear localization signal, is essential for the intracrine stimulation of proliferation in vascular smooth muscle cells
De Miguel, F
Fiaschi-Taesch, N
López-Talavera, JC
Takane, KK
Massfelder, T
Helwig, JJ
Stewart, AF
[J]. ENDOCRINOLOGY, 2001, 142 (09) : 4096 - 4105
[10] Fassina G, 1996, INT J ONCOL, V8, P253

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