Related Experiment Video
Updated: Aug 7, 2026
06:48
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Protein changes associated with ionizing radiation-induced apoptosis in human prostate epithelial tumor cells
S C Prasad1, V A Soldatenkov, M R Kuettel
1Department of Radiation Medicine, Vincent T. Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007-2197, USA. prasads@gunet.georgetown.edu
Electrophoresis
|May 27, 1999
Summary
Ionizing radiation (IR) therapy for prostate cancer causes cell death by altering protein levels. Key intermediate filament proteins decrease while chaperone proteins accumulate during IR-induced apoptosis.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Ionizing radiation (IR) is a crucial treatment for localized prostate cancer.
- Understanding protein changes during IR-induced apoptosis is vital for comprehending cancer cell death.
- Prostate cancer cells undergo programmed cell death (apoptosis) when exposed to IR.
Purpose of the Study:
- To identify protein alterations during the execution phase of IR-induced apoptosis in prostate cancer cells.
- To characterize the metabolic status of dying prostate cancer cells.
- To investigate the role of intermediate filament proteins and molecular chaperones in IR-induced apoptosis.
Main Methods:
- Utilized an in vitro model of radiation-transformed human prostate epithelial cells (267B1-XR).
- Applied analytical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE).
- Confirmed protein changes using Western blotting with specific antisera.
Main Results:
- Significant reduction in intermediate filament proteins (keratins-18, 19, vimentin) and 14-3-3 adapter proteins observed.
- Marked accumulation of molecular chaperones (glucose-regulated protein 94, calreticulin, calnexin, protein disulfide isomerase) in dying cells.
- Evidence of specific proteolysis solubilizing intermediate filaments and increased endoplasmic reticulum (ER) chaperone proteins.
Conclusions:
- Apoptosis in prostate cancer cells involves the breakdown of intermediate filament networks.
- Increased levels of ER chaperone proteins are associated with IR-induced cell death.
- These protein profile changes provide insights into the cellular mechanisms of prostate cancer therapy response.
Related Concept Videos
02:23Abnormal 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...
02:07Tumor 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...
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...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:19Interactions 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...
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...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...