Human prostate cancer expresses the low affinity insulin-like growth factor binding protein IGFBP-rP1

A Degeorges1, F Wang, H F Frierson

  • 1Department of Urology, Molecular Urology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

Cancer Research
|June 26, 1999
PubMed

Insights

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is found in prostate cancer but not normal tissue. Its expression can be induced in cancer cells within the body, suggesting a role in tumor development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Endocrinology

Background:

  • Alterations in the insulin-like growth factor (IGF) axis are linked to prostate disease.
  • Insulin-like growth factor binding proteins (IGFBPs) modulate IGF actions.
  • IGFBP-related protein 1 (IGFBP-rP1), also known as IGFBP-7, is a newly identified IGFBP family member with an unclear biological function.

Purpose of the Study:

  • To investigate the localization of IGFBP-rP1 in prostate cancer and benign prostate tissues.
  • To analyze the expression of IGFBP-rP1 in prostate cancer cell lines and in vivo models.

Main Methods:

  • Immunohistochemistry using a specific polyclonal antibody (T1A12) to detect IGFBP-rP1.
  • Northern blot analysis to assess IGFBP-rP1 mRNA expression in prostate cancer cell lines.
  • Analysis of tumor xenografts generated from prostate cancer cell lines in vivo.

Main Results:

  • IGFBP-rP1 staining was intense in nerves and weak in smooth muscle cells; lymphocytes were negative.
  • Normal prostatic secretory epithelium and benign prostatic hyperplasia (BPH) epithelium showed little to no IGFBP-rP1 staining.
  • Positive IGFBP-rP1 staining was observed in 90.5% of primary adenocarcinomas and 100% of metastases.
  • Prostate cancer cell lines did not express IGFBP-rP1 mRNA in vitro.
  • IGFBP-rP1 expression was induced in vivo in tumor xenografts when prostate cancer cells interacted with the host environment, particularly in bone marrow.

Conclusions:

  • IGFBP-rP1 is expressed in both in situ and invasive prostate neoplasms, distinguishing them from normal or hyperplastic epithelium.
  • The expression of IGFBP-rP1 can be induced in human prostate cancer cell lines in vivo, suggesting a role for the host microenvironment.
  • IGFBP-rP1 may serve as a potential biomarker or therapeutic target in prostate cancer.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...