A 38-year-old woman presents to her physician to discuss genetic testing. She has no past medical history, but her mother died of breast cancer at age 42 years, and her sister was diagnosed with ovarian cancer at age 44 years. Genetic testing is ordered and reveals a mutation in the HER2 gene. Breast cancer is often caused by a mutation in the HER2 receptor/signaling mechanism.
D) RTK/Ras/MAPK
There are many signaling mechanisms throughout human physiology. Some of these are implicated in disease processes when genetic mutations occur. The HER2 gene is part of the human epidermal growth factor family and codes for a receptor called Ras Tyrosine Kinase (RTK) transmembrane protein. The RTK signal, when activated, phosphorylates the Ras protein, which sets of a signaling cascade that also operates through the Map Kinase protein. The end result is increased transcription of genes involves in cell cycle progression and cell proliferation.
A common mutation of the HER2 gene is the HER2/neu mutation, which creates a constitutively activated protein. The result is unopposed cell proliferation and differentiation, a hallmark of cancer. This mutation is commonly found in certain types of breast cancer. Cancers of this type can often be successfully treated with the monoclonal protein trastuzumab.
Answer A: Adenylyl cyclase/cAMP/PKA, is incorrect. Adenylyl cyclase/cAMP/PKA is involved in cellular metabolism.
Answer B: Guanalyl cyclase/cGMP/PKG, is incorrect. Guanalyl cyclase/cGMP/PKG is involved in smooth muscular and vasculature.
Answer C: JAK/STAT, is incorrect. JAK/STAT is involved in cell apoptosis.
Answer E: TGF-beta/Smad, is incorrect. TGF-beta/Smad is involved in the immune system.
Key Learning Point
The RTK/Ras/MAPK signaling pathway is affected by HER2 mutations and is commonly found in certain types of breast cancer.
