1. • Breast cancer is among the most prevalent of all cancers, second only to lung cancer.
• Mitochondrial morphological analyses of length shows the HTB-22 (adenocarcinoma)
displays a pro-fission phenotype with the shortest mitochondrial length observed.
• Breast cancer is among the most prevalent of all cancers, second only to lung cancer.
• Mitochondrial morphological analyses of length shows the HTB-22 (adenocarcinoma)
displays a pro-fission phenotype with the shortest mitochondrial length observed.
A Comparison of Mitochondrial Morphology in Breast Cancer Models
Zachary V. Gardner and Emily R. Roberts
Biological Sciences Department, Colorado Mesa University
A Comparison of Mitochondrial Morphology in Breast Cancer Models
Zachary V. Gardner and Emily R. Roberts
Biological Sciences Department, Colorado Mesa University
• Breast cancer is among the most prevalent of all cancers, second only to lung cancer.
• Mitochondria constantly undergo fusion and fission processes into longer and shorter
versions of these organelles, a process called mitochondrial dynamics.
• Mitochondrial dynamics and its role in breast cancer tumorigenesis is poorly characterized.
• This study investigated the dynamic nature of mitochondria and its role in human breast
cancer cell lines to determine how mitochondrial fusion and the fission influences cellular
death, including apoptosis, mitophagy, and survival (See Refs).
• Breast cancer is among the most prevalent of all cancers, second only to lung cancer.
• Mitochondria constantly undergo fusion and fission processes into longer and shorter
versions of these organelles, a process called mitochondrial dynamics.
• Mitochondrial dynamics and its role in breast cancer tumorigenesis is poorly characterized.
• This study investigated the dynamic nature of mitochondria and its role in human breast
cancer cell lines to determine how mitochondrial fusion and the fission influences cellular
death, including apoptosis, mitophagy, and survival (See Refs).
Figure 1. Mitochondrial dynamics showing fusion and fission via multi-protein pathways.
• Cancers exhibit an ability to evade apoptosis (controlled by the mitochondria).
• Mitochondrial fusion is linked to apoptotic inhibition (survival).
• Mitochondrial fission is essential for apoptosis (programmed cell death).
• As such, breast cancer models HTB-22 (adenocarcinoma) and HTB-126 (invasive ductal
carcinoma) should exhibit pro-fusion mitochondrial phenotypes when compared to HTB-
125 (non-tumorigenic lung epithelial cell) that will correlate with cancer cell survival.
• Cells were cultured in Opti-MEM with 10% fetal bovine serum and 5% CO2.
• Mitochondria were stained using Mitotracker Orange (Invitrogen), fixed with 4%
paraformaldehyde and visualized with the Texas Red filter using spinning disk confocal
microscopy (100x magnification).
• Mitochondrial length (N=94-96) measured in pixels using ImageJ software and converted
to microns using a corrective conversion factor (0.1402 µm/pixel).
• Statistical analyses: One-way ANOVA with Bonferroni post-tests.
HTB-125
HTB-126
HTB-22
MethodsMethods
Introduction
Hypothesis
Results
Conclusions
Future Directions
ReferencesReferences
• No significant differences in mitochondrial length were observed between the invasive
ductal carcinoma cells and the normal epithelial cells of the breast.
• HTB-126 did not show the hypothesized pro-fusion phenotype.
• The dynamic nature of mitochondria does not contribute to tumorigenesis of HTB-126
cells but the data supports a potential alteration of HTB-22 cells.
• Focus on adenocarcinoma (HTB-22) cells as they display a phenotype that could
potentially be influenced by alterations in mitochondrial dynamics.
• Examine post-fission mediated apoptotic signaling pathways that are controlled by the
pro-fission protein, Drp1 (Dynamin-related protein 1) via confocal microscopy and
Western blot analyses.
Figure 1. Thomas KJ and Cookson MR (2009). The Role of PTEN-induced Kinase 1 in
Mitochondrial Dysfunction and Dynamics. Int J Biochem Cell Biol. 41(10): 2025-35.
Figure 2.
http://www.bccancer.bc.ca/HPI/Nursing/Education/breastcancer/diagnosis/bcbasics.htm
Thomas KJ and MR Jacobson (2012). Defects in Mitochondrial Fission Protein Dynamin-
Related Protein 1 (Drp1) are Linked to Apoptotic Resistance and Autophagy in a Lung
Cancer Model. PLoS One. 7(9): e45319.
Roberts ER, Thomas KJ (2013). The Role of Mitochondria in the Development and
Progression of Lung Cancer. Comput Struct Biotechnol J. 6 (7): e201303019.
Figure 2. Breast Anatomy and Tumorigenic Conversion of its Cells.
TumorigenicConversion
HTB-125
HTB-22
HTB-126
HTB-22
HTB-125
HTB-126
Zoom of morphology
• Mentored by Dr. Kelly Jean Thomas Craig.
AcknowledgementAcknowledgement