Related Experiment Video

Updated: Jul 30, 2026

Murine Prostate Micro-dissection and Surgical Castration
08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

Regulation of prostate cell growth and morphogenesis by Dickkopf-3

Y Kawano1, M Kitaoka, Y Hamada

  • 11Prostate Cancer Research Group, Harris Laboratory, Department of Oncology, Division of SORA, Imperial College London, London, UK.

Oncogene
|June 6, 2006
PubMed

Insights

Loss of Dickkopf-3 (Dkk-3) expression in prostate cancer impairs glandular structure and promotes uncontrolled cell proliferation. Restoring Dkk-3 expression inhibits cancer cell growth and differentiation, suggesting its tumor-suppressive role.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Wnt signaling is crucial in cancer development.
  • Secreted Wnt antagonists, like Dickkopfs (Dkks), negatively regulate Wnt signaling.
  • Reduced Dkk family expression is observed in various cancers.

Purpose of the Study:

  • To investigate the role of Dkk-3 in prostate cancer.
  • To determine the effect of Dkk-3 expression levels on prostate cancer cell behavior.
  • To explore Dkk-3's function in prostate epithelial cell differentiation and glandular structure.

Main Methods:

  • Comparison of Dkk-3 expression in normal vs. prostate cancer cells.
  • Ectopic and inducible expression of Dkk-3 in prostate cancer cell lines (LNCaP, PC3).
  • Small interfering RNA (siRNA)-mediated Dkk-3 downregulation in normal prostate epithelial cells (RWPE-1).
  • Immunohistochemical analysis of Dkk-3 in prostate tissues.
  • Three-dimensional cell culture to assess acinar morphogenesis.

Main Results:

  • Dkk-3 expression is reduced in prostate cancer cells, especially high-grade tumors.
  • Ectopic Dkk-3 expression inhibited colony formation and proliferation in cancer cells.
  • Dkk-3 downregulation enhanced cell cycle progression in normal prostate cells.
  • Dkk-3 depletion disrupted acinar morphogenesis in a 3D model.
  • Reduced Dkk-3 expression correlates with impaired glandular structure and uncontrolled PrEC proliferation.

Conclusions:

  • Loss of Dkk-3 expression contributes to prostate cancer progression by disrupting glandular structure and promoting proliferation.
  • Dkk-3 acts as a tumor suppressor in the prostate.
  • Dkk-3 may play a role in prostate epithelial cell differentiation and maintaining tissue architecture.

More Related Videos

Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture10:38

Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture

Published on: November 22, 2019

Generation of a Mouse Prostate Organoid-Based Model for Studying Host-Pathogen Interactions08:05

Generation of a Mouse Prostate Organoid-Based Model for Studying Host-Pathogen Interactions

Published on: February 27, 2026

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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...