Related Experiment Video

Updated: Jun 11, 2026

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Clinicopathologic and molecular significance of phospho-Akt expression in early invasive breast cancer

Mohammed A Aleskandarany1, Emad A Rakha, Mohamed A Ahmed

  • 1Division of Pathology, School of Molecular Medical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.

Breast Cancer Research and Treatment
|July 10, 2010
PubMed

Insights

Phospho-Akt1 (pAkt) is frequently overexpressed in breast cancer but not a direct prognostic marker. However, combined PIK3CA and pAkt expression defines tumor phenotypes impacting patient survival, guiding targeted therapy development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The Akt/PKB pathway is crucial for cell metabolism, growth, proliferation, and survival.
  • Targeted therapies for breast cancer are challenged by the complexity of the Akt pathway.
  • Understanding Akt pathway activation is key to developing effective breast cancer treatments.

Purpose of the Study:

  • To investigate the expression of phospho-Akt1 (pAkt) in early invasive breast cancer.
  • To correlate pAkt expression with upstream/downstream pathway proteins, clinicopathologic features, and patient outcomes.
  • To identify distinct tumor phenotypes based on PIK3CA and pAkt expression and their prognostic significance.

Main Methods:

  • Immunohistochemistry was used to evaluate pAkt (Ser473) expression in 1,202 early invasive breast cancer tissue microarrays.
  • Analysis included correlations with estrogen/androgen receptors, PIK3CA, cytokeratins (CK18, CK19), PTEN, CK5/6, p53, and Ki67.
  • Patient outcomes, including breast cancer-specific survival (BCSS) and metastasis-free survival (MFS), were assessed.

Main Results:

  • Seventy-six percent of tumors overexpressed pAkt, associated with hormone receptors, PIK3CA, CK18, CK19, and PTEN.
  • Loss of pAkt correlated with high grade, CK5/6, p53, and high Ki67; luminal tumors showed higher pAkt positivity than triple-negative/basal subtypes.
  • pAkt overexpression alone did not predict BCSS or MFS, but four PIK3CA/pAkt combinatorial phenotypes significantly impacted both BCSS and MFS.

Conclusions:

  • While pAKT is an oncogene linked to adverse prognostic factors, it is not an independent prognostic marker in breast cancer.
  • Combinatorial PIK3CA/pAkt expression defines distinct tumor phenotypes with significant prognostic value.
  • These findings highlight the functional complexity of the Akt pathway and can inform the development of targeted therapeutic strategies for specific breast cancer subgroups.

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...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...