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Characterization of insulin-like growth factor-binding protein-related proteins (IGFBP-rPs) 1, 2, and 3 in human prostate epithelial cells: potential roles for IGFBP-rP1 and 2 in senescence of the prostatic epithelium.

Publication ,  Journal Article
López-Bermejo, A; Buckway, CK; Devi, GR; Hwa, V; Plymate, SR; Oh, Y; Rosenfeld, RG
Published in: Endocrinology
November 2000

Insulin-like growth factor (IGF)-binding protein (IGFBP)-related proteins (IGFBP-rPs) are newly described cysteine-rich proteins that share significant aminoterminal structural similarity with the conventional IGFBPs and are involved in a diversity of biological functions, including growth regulation. IGFBP-rP1 (MAC25/Angiomodulin/prostacyclin-stimulating factor) is a potential tumor-suppressor gene that is differentially expressed in meningiomas, mammary and prostatic cancers, compared with their malignant counterparts. We have previously shown that IGFBP-rP1 is preferentially produced by primary cultures of human prostate epithelial cells (HPECs) and by poorly tumorigenic P69SV40T cells, compared with the cancerous prostatic LNCaP, DU145, PC-3, and M12 cells. We now show that IGFBP-rP1 increases during senescence of HPEC. IGFBP-rP2 (also known as connective tissue growth factor), a downstream effector of transforming growth factor (TGF)-beta and modulator of growth for both fibroblasts and endothelial cells, was detected in most of the normal and malignant prostatic epithelial cells tested, with a marked up-regulation of IGFBP-rP2 during senescence of HPEC. Moreover, IGFBP-rP2 noticeably increased in response to TGF-beta1 and all-trans retinoic acid (atRA) in HPEC and PC-3 cells, and it decreased in response to IGF-I in HPEC. IGFBP-rP3 [nephroblastoma overexpressed (NOV)], the protein product of the NOV protooncogene, was not detected in HPEC but was expressed in the tumorigenic DU145 and PC-3 cells. It was also synthesized by the SV40-T antigen-transformed P69 and malignant M12 cells, where it was down-regulated by atRA. These observations suggest biological roles of IGFBP-rPs in the human prostate. IGFBP-rP1 and IGFBP-rP2 are likely to negatively regulate growth, because they seem to increase during senescence of the prostate epithelium and in response to growth inhibitors (TGF-beta1 and atRA). Although the data collected on IGFBP-rP3 in prostate are modest, its role as a growth stimulator and/or protooncogene is supported by its preferential expression in cancerous cells and its down-regulation by atRA.

Duke Scholars

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

November 2000

Volume

141

Issue

11

Start / End Page

4072 / 4080

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Tretinoin
  • Transforming Growth Factor beta
  • Time Factors
  • RNA, Messenger
  • Prostate
  • Mice
  • Male
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Protein 3
 

Citation

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López-Bermejo, A., Buckway, C. K., Devi, G. R., Hwa, V., Plymate, S. R., Oh, Y., & Rosenfeld, R. G. (2000). Characterization of insulin-like growth factor-binding protein-related proteins (IGFBP-rPs) 1, 2, and 3 in human prostate epithelial cells: potential roles for IGFBP-rP1 and 2 in senescence of the prostatic epithelium. Endocrinology, 141(11), 4072–4080. https://doi.org/10.1210/endo.141.11.7783
López-Bermejo, A., C. K. Buckway, G. R. Devi, V. Hwa, S. R. Plymate, Y. Oh, and R. G. Rosenfeld. “Characterization of insulin-like growth factor-binding protein-related proteins (IGFBP-rPs) 1, 2, and 3 in human prostate epithelial cells: potential roles for IGFBP-rP1 and 2 in senescence of the prostatic epithelium.Endocrinology 141, no. 11 (November 2000): 4072–80. https://doi.org/10.1210/endo.141.11.7783.
Journal cover image

Published In

Endocrinology

DOI

ISSN

0013-7227

Publication Date

November 2000

Volume

141

Issue

11

Start / End Page

4072 / 4080

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Tretinoin
  • Transforming Growth Factor beta
  • Time Factors
  • RNA, Messenger
  • Prostate
  • Mice
  • Male
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor Binding Protein 3