Parathyroid hormone-related protein upregulates integrin expression via an intracrine pathway in PC-3 prostate cancer cells

Xiaoli Shen, Miriam Falzon

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Parathyroid hormone-related protein (PTHrP) is expressed by human prostatic tissue and prostate cancer cell lines, and enhances prostate tumor cell growth both in vivo and in vitro. PTHrP expression also plays a role in the development of bone metastasis, which is a frequent complication in patients with prostate carcinoma. Tumor cell adhesion to extracellular matrix (ECM) components is mediated via integrin subunits, and plays a major role in the invasion and metastasis of tumor cells. We previously showed that PTHrP overexpression increases adhesion of the human prostate cancer cell line PC-3 to the ECM molecules collagen type I, fibronectin, and laminin. Increased adhesion is accompanied by upregulation in the expression of α1, α5, α6, and β4 integrin subunits. We used the same cell line to study the mechanism via which PTHrP upregulates integrin expression. Clonal PC-3 cells were established overexpressing wild-type PTHrP or PTHrP mutated in the nuclear localization sequence (NLS). Mutation of the NLS negated the effects of PTHrP on α1, α5, α6, and β4 integrin expression, indicating that these effects are mediated via an intracrine pathway requiring nuclear localization. Expression of the α2, α3, αv, and β1 integrin subunits were comparable in wild-type and NLS-mutated PTHrP transfectants. These findings indicate that PTHrP may play a role in prostate tumor invasion and metastasis by upregulating the expression of specific integrin subunits via an intracrine pathway.

Original languageEnglish (US)
Pages (from-to)17-29
Number of pages13
JournalRegulatory Peptides
Volume113
Issue number1-3
DOIs
StatePublished - May 15 2003

Fingerprint

Parathyroid Hormone-Related Protein
Integrins
Prostatic Neoplasms
Up-Regulation
Cells
Tumors
Prostate
Neoplasm Metastasis
Cell Line
Extracellular Matrix
Neoplasms
Adhesion
Bone Development
Cell adhesion
Cell growth
Laminin
Collagen Type I
Fibronectins
Cell Adhesion
Bone

Keywords

  • FACS analysis
  • Integrin
  • Nuclear localization sequence
  • Transfection

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Parathyroid hormone-related protein upregulates integrin expression via an intracrine pathway in PC-3 prostate cancer cells. / Shen, Xiaoli; Falzon, Miriam.

In: Regulatory Peptides, Vol. 113, No. 1-3, 15.05.2003, p. 17-29.

Research output: Contribution to journalArticle

@article{87bbc12d5bf74027a86f19ce77849bc9,
title = "Parathyroid hormone-related protein upregulates integrin expression via an intracrine pathway in PC-3 prostate cancer cells",
abstract = "Parathyroid hormone-related protein (PTHrP) is expressed by human prostatic tissue and prostate cancer cell lines, and enhances prostate tumor cell growth both in vivo and in vitro. PTHrP expression also plays a role in the development of bone metastasis, which is a frequent complication in patients with prostate carcinoma. Tumor cell adhesion to extracellular matrix (ECM) components is mediated via integrin subunits, and plays a major role in the invasion and metastasis of tumor cells. We previously showed that PTHrP overexpression increases adhesion of the human prostate cancer cell line PC-3 to the ECM molecules collagen type I, fibronectin, and laminin. Increased adhesion is accompanied by upregulation in the expression of α1, α5, α6, and β4 integrin subunits. We used the same cell line to study the mechanism via which PTHrP upregulates integrin expression. Clonal PC-3 cells were established overexpressing wild-type PTHrP or PTHrP mutated in the nuclear localization sequence (NLS). Mutation of the NLS negated the effects of PTHrP on α1, α5, α6, and β4 integrin expression, indicating that these effects are mediated via an intracrine pathway requiring nuclear localization. Expression of the α2, α3, αv, and β1 integrin subunits were comparable in wild-type and NLS-mutated PTHrP transfectants. These findings indicate that PTHrP may play a role in prostate tumor invasion and metastasis by upregulating the expression of specific integrin subunits via an intracrine pathway.",
keywords = "FACS analysis, Integrin, Nuclear localization sequence, Transfection",
author = "Xiaoli Shen and Miriam Falzon",
year = "2003",
month = "5",
day = "15",
doi = "10.1016/S0167-0115(02)00293-8",
language = "English (US)",
volume = "113",
pages = "17--29",
journal = "Regulatory Peptides",
issn = "0167-0115",
publisher = "Elsevier",
number = "1-3",

}

TY - JOUR

T1 - Parathyroid hormone-related protein upregulates integrin expression via an intracrine pathway in PC-3 prostate cancer cells

AU - Shen, Xiaoli

AU - Falzon, Miriam

PY - 2003/5/15

Y1 - 2003/5/15

N2 - Parathyroid hormone-related protein (PTHrP) is expressed by human prostatic tissue and prostate cancer cell lines, and enhances prostate tumor cell growth both in vivo and in vitro. PTHrP expression also plays a role in the development of bone metastasis, which is a frequent complication in patients with prostate carcinoma. Tumor cell adhesion to extracellular matrix (ECM) components is mediated via integrin subunits, and plays a major role in the invasion and metastasis of tumor cells. We previously showed that PTHrP overexpression increases adhesion of the human prostate cancer cell line PC-3 to the ECM molecules collagen type I, fibronectin, and laminin. Increased adhesion is accompanied by upregulation in the expression of α1, α5, α6, and β4 integrin subunits. We used the same cell line to study the mechanism via which PTHrP upregulates integrin expression. Clonal PC-3 cells were established overexpressing wild-type PTHrP or PTHrP mutated in the nuclear localization sequence (NLS). Mutation of the NLS negated the effects of PTHrP on α1, α5, α6, and β4 integrin expression, indicating that these effects are mediated via an intracrine pathway requiring nuclear localization. Expression of the α2, α3, αv, and β1 integrin subunits were comparable in wild-type and NLS-mutated PTHrP transfectants. These findings indicate that PTHrP may play a role in prostate tumor invasion and metastasis by upregulating the expression of specific integrin subunits via an intracrine pathway.

AB - Parathyroid hormone-related protein (PTHrP) is expressed by human prostatic tissue and prostate cancer cell lines, and enhances prostate tumor cell growth both in vivo and in vitro. PTHrP expression also plays a role in the development of bone metastasis, which is a frequent complication in patients with prostate carcinoma. Tumor cell adhesion to extracellular matrix (ECM) components is mediated via integrin subunits, and plays a major role in the invasion and metastasis of tumor cells. We previously showed that PTHrP overexpression increases adhesion of the human prostate cancer cell line PC-3 to the ECM molecules collagen type I, fibronectin, and laminin. Increased adhesion is accompanied by upregulation in the expression of α1, α5, α6, and β4 integrin subunits. We used the same cell line to study the mechanism via which PTHrP upregulates integrin expression. Clonal PC-3 cells were established overexpressing wild-type PTHrP or PTHrP mutated in the nuclear localization sequence (NLS). Mutation of the NLS negated the effects of PTHrP on α1, α5, α6, and β4 integrin expression, indicating that these effects are mediated via an intracrine pathway requiring nuclear localization. Expression of the α2, α3, αv, and β1 integrin subunits were comparable in wild-type and NLS-mutated PTHrP transfectants. These findings indicate that PTHrP may play a role in prostate tumor invasion and metastasis by upregulating the expression of specific integrin subunits via an intracrine pathway.

KW - FACS analysis

KW - Integrin

KW - Nuclear localization sequence

KW - Transfection

UR - http://www.scopus.com/inward/record.url?scp=0037447758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037447758&partnerID=8YFLogxK

U2 - 10.1016/S0167-0115(02)00293-8

DO - 10.1016/S0167-0115(02)00293-8

M3 - Article

VL - 113

SP - 17

EP - 29

JO - Regulatory Peptides

JF - Regulatory Peptides

SN - 0167-0115

IS - 1-3

ER -