Related Experiment Video

Updated: Jul 5, 2026

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
08:36

Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses

Published on: October 24, 2019

AKT regulates androgen receptor-dependent growth and PSA expression in prostate cancer

Margarita Mikhailova1, Yu Wang, Roble Bedolla

  • 1Research Services, VA Northern California HCS, Mather, CA, USA.

Advances in Experimental Medicine and Biology
|May 24, 2008
PubMed

Insights

Androgen deprivation therapy failure in recurrent prostate cancer (PC) may involve increased Akt activation. Akt promotes cell survival independently of the androgen receptor (AR), suggesting an alternative pathway for PC to resist treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Recurrent prostate cancer (PC) is often treated with androgen deprivation therapy (ADT).
  • ADT initially succeeds but frequently fails due to the emergence of androgen-independent PC.
  • Akt signaling, a key regulator of cell growth and survival, is activated by ADT.

Purpose of the Study:

  • To investigate if increased Akt phosphorylation contributes to the development of androgen independence in PC.
  • To elucidate the role of Akt in regulating androgen receptor (AR) transcriptional activity.
  • To differentiate the roles of Akt in androgen-sensitive versus androgen-insensitive PC proliferation and survival.

Main Methods:

  • Analysis of Akt phosphorylation levels under androgen deprivation.
  • Assessment of Akt's influence on androgen receptor (AR) transcriptional activity.
  • Evaluation of Akt's role in prostate cancer cell proliferation and survival under varying androgen conditions.

Main Results:

  • Androgen deprivation significantly increases Akt phosphorylation (activation).
  • Akt-stimulated AR transcriptional activity requires androgen binding.
  • While the androgen-sensitive proliferation is Akt-dependent, the androgen-insensitive component is not.
  • Akt-induced cell survival is largely independent of the AR.

Conclusions:

  • Increased Akt phosphorylation is implicated in the development of androgen independence in prostate cancer.
  • Prostate cancer cells may utilize Akt activation as an alternative survival pathway during androgen deprivation.
  • Targeting Akt signaling could be a potential strategy to overcome ADT resistance in recurrent PC.

More Related Videos

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer07:25

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

Published on: March 6, 2018

An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

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...
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...
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...
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...
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.
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...