Activation of c-Src is inversely correlated with biological aggressiveness of breast carcinoma

Yasuhiro Ito1, Hisaaki Kawakatsu, Tsutomu Takeda

  • 1Department of Surgery, Osaka Seamen's Insurance Hospital, Suita, Osaka, Japan.

Insights

Activated c-Src was detected in over half of breast carcinoma tissues, inversely correlating with aggressive tumor features. This suggests activated c-Src may be linked to less aggressive breast cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • c-Src is a non-receptor protein tyrosine kinase implicated in cellular signaling.
  • Aberrant Src kinase activity is observed in various human cancers, including breast carcinoma.
  • Understanding the role of activated c-Src in breast cancer progression is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the involvement of activated c-Src in the carcinogenesis and progression of human breast carcinoma.
  • To correlate the expression of activated c-Src with clinicopathological features of breast cancer.

Main Methods:

  • Western blotting was used to confirm antibody specificity against activated c-Src (Clone 28) in breast carcinoma cell lines.
  • Immunofluorescence analysis localized activated c-Src within the cytoplasm of carcinoma cells.
  • Immunohistochemical staining was performed on 73 human breast carcinoma tissue specimens.

Main Results:

  • Activated c-Src was detected in 50.7% (37/73) of breast carcinoma tissues.
  • Positive staining for activated c-Src was inversely correlated with Ki-67 labeling index, TNM stage, tumor size, and histological grade.
  • Normal mammary gland cells and stromal cells adjacent to carcinoma were negative for activated c-Src.

Conclusions:

  • The activation of c-Src is associated with breast carcinomas exhibiting lower aggressiveness.
  • Activated c-Src expression may serve as a potential biomarker for less aggressive breast cancer subtypes.
  • Further research is warranted to elucidate the precise mechanisms by which c-Src influences breast cancer progression.

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...
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...
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...
Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...