TBL Breast Mass Flashcards
Growth factors
Capable of stimulating cell growth, proliferation, and differentiation
Epidermal growth factors (EGF) (function and structural features)
Induce proliferation in epidermal cells. Have high binding affinity for EGFR (epidermal growth factor receptor). Produces mitogenic response (encourages proliferation) in EGF-receptive cells. Have 6 cysteine residues.
What happens when EGF binds to EGFR? (3 steps)
- Stimulates protein-tyrosine kinase activity of receptor 2. This initiates a signal cascade leading to increases in intracellular Ca2+, increases glycolysis and protein synthesis, and increases expression of certain genes (including EGFR gene) 3. DNA synthesis and cell proliferation
Mitogenic response
Cell proliferation in reponse to mitogens
Mitogen
Chemical that triggers mitosis by activating signal transduction pathways in which mitogen-activated protein kinase (MAP kinase) is involved
ErbB family of receptors
EGFR (aka HER1, ErbB-1), HER2/c-neu (aka ErbB-2), HER3 (aka ErbB-3), HER4 (aka ErbB-4)
HER2 vs HER2
If not in italics referring to the protein, if in italics referring to the gene
Proto-oncogene
Normal gene which regulates cell growth
HER2 (gene)
Proto-oncogene on chromosome 17. Considered an oncogene when it leads to transformation for cells and uncontrolled cell growth.
HER2 (protein) names
Named because of similar structure to Human Epidermal growth factor Receptor 2. neu orginally identified in neuroglioblastoma cell lines. ErbB-2 named for similarity to ErbB (avian erythroblastosis oncogene B).
Overexpression of HER2 (prevalence in breast cancer and consequences)
Happens in ~15% of breast cancers. Causes increased signal transduction resulting in rapid cell division and tumor growth.
HER pathway
- EGF binds to EGFR (HER-2 protein) 2. Receptors dimerize and activate tyrosine kinase 3. Ras and MAP kinase are signaled 4. MAP kinase transported to the nucleus where genes are activated leading to mitosis
How is the HER signaling cascade inactivated? (2 ways)
- Remove receptors on the cell through endocytosis and degredation 2. Use an antagonist molecule which will bind to the EGFR receptor but not initiate signal transduction
HER2 (gene) in normal cells
1 copy of HER2 on each copy of chromosome 17. Expression of this gene in normal breast epithelial cells gives rise to transmembrane protein growth factor receptor with tyrosine kinase activity.
HER2+ mutation
HER2 gene amplified 2-20x in each tumor cell nucleus. Amplification drives protein overexpression leading to increased number of receptors at the tumor-cell surface (2 million vs normal 20,000). Receptor activation is promoted leading to signaling, excessive cell division, and formation of tumors.
Oncogene
Gene that has the potential to cause cancer if mutated or expressed abnormally
Most common sites of metastasis in breast cancer
Lymph nodes near breast, bones, liver, lungs, and brain
Composition of metastatic tumors
Has same kind of abnormal cells as primary tumor (if breast cancer cells move to bone it’s still breast cancer, not called bone cancer)
Breast Cancer Stage 0
Carcinoma is in situ and non-invasive (ex. ductal carcinoma in situ: abnormal cells in the lining of a duct)
Breast Cancer Stage 1
Early stage of invasive breast cancer. Cancer cells have not spread beyond breast.
Breast Cancer Stage 2
Tumor is 2-5cm and has spread to lymph nodes under the arm
Breast Cancer Stage 3
Locally advanced cancer. Tumor has spread to underarm lymph nodes and to lymph nodes behind the breastbone
Breast Cancer Stage 4
Distant metastatic cancer. Cancer has spread to other parts of the body (bone, liver, lungs)
Recurrent cancer
Cancer that has come back after a period of time when it could not be detected. It may recur locally in the breast or chest wall or it may recur in any other part of the body.
