Related Experiment Video

Updated: Apr 16, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

14.0K

Mechanistic rationale for MCL1 inhibition during androgen deprivation therapy

Frédéric R Santer1, Holger H H Erb1,2, Su Jung Oh1

  • 1Medical University of Innsbruck, Department of Urology, Division of Experimental Urology, Innsbruck, Austria.

Oncotarget
|March 10, 2015
PubMed

Insights

MCL1 protein prevents cell death in prostate cancer (PCa) during androgen deprivation therapy. Targeting MCL1 with Obatoclax may improve treatment outcomes for advanced PCa.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Androgen deprivation therapy (ADT) is a cornerstone in prostate cancer (PCa) treatment.
  • Resistance to ADT, leading to castration-resistant PCa (CRPC), remains a significant clinical challenge.
  • MCL1 is implicated in chemotherapy resistance, but its role in cellular response to androgen withdrawal is unclear.

Purpose of the Study:

  • To investigate the role of MCL1 in regulating prostate cancer cell fate under androgen-deprived conditions.
  • To determine if MCL1 expression is modulated by androgen receptor (AR) signaling.
  • To evaluate the therapeutic potential of targeting MCL1 in PCa.

Main Methods:

  • Analysis of MCL1 protein and mRNA expression in PCa tissues and cell lines.
  • In vitro and in vivo studies using PCa cellular models.
  • Manipulation of MCL1 expression (downregulation/overexpression) and treatment with BH3-mimetic Obatoclax.

Main Results:

  • MCL1 expression is higher in cancerous versus benign prostate tissue and upregulated in androgen-deprived PCa cells.
  • MCL1 upregulation is indirectly mediated via AR signaling and cell cycle-dependent mechanisms.
  • MCL1 overexpression prevents apoptosis in androgen-deprived PCa cells; Obatoclax induces apoptosis and decreases MCL1 in sensitive cells, while resistant cells upregulate MCL1.
  • Obatoclax shows synergistic effects with AR inactivation and inhibits clonogenicity of basal PCa cells.

Conclusions:

  • MCL1 is a critical determinant of prostate cancer cell survival during androgen deprivation.
  • MCL1 represents a potential therapeutic target for overcoming resistance to ADT.
  • Targeting MCL1, potentially in combination with AR-targeting therapies, may offer new treatment strategies for advanced prostate cancer.
Keywords:
BCL2 familycell cycle arrestcell deathendocrine therapytreatment resistance

More Related Videos

Murine Prostate Micro-dissection and Surgical Castration08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

48.3K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.9K

Related Concept Videos

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...
5.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.3K
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...
5.5K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.5K