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Breast cancer is associated with loss of the c-kit oncogene product
P G Natali1, M R Nicotra, I Sures
1Department of Immunology, Regina Elena Cancer Institute, Rome, Italy.
Abstract:
The proto-oncogene c-kit encodes a tyrosine kinase receptor related to the PDGF/CSF-1 receptors. Mutations of this gene result in impairment of hematopoiesis, melanogenesis and gametogenesis. Using monoclonal antibodies to the c-kit gene product, we have analyzed its expression in normal and transformed human tissues. Unexpectedly, the receptor was found to be expressed in normal mammary epithelium. While in benign breast lesions, the c-kit gene product was detected at variable levels in 82% of the instances, in primary tumors, no product could be identified in 87% of the cases. This phenotype is maintained in metastatic foci. These findings were confirmed by paired Northern blot analysis of RNA preparations from normal and tumor tissues. These results demonstrate that the c-kit receptor may also be involved in the growth control of mammary epithelium and that this function may be impaired following malignant transformation and de-differentiation.
Insights
The c-kit receptor is present in normal breast tissue but lost in most breast cancers. This suggests c-kit
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The proto-oncogene c-kit encodes a tyrosine kinase receptor.
- Mutations in c-kit are linked to impaired hematopoiesis, melanogenesis, and gametogenesis.
- The role of c-kit in mammary epithelium was previously unclear.
Purpose of the Study:
- To investigate the expression of the c-kit receptor in normal and malignant human breast tissues.
- To determine if c-kit expression changes during breast cancer development and progression.
Main Methods:
- Utilized monoclonal antibodies to detect the c-kit gene product.
- Analyzed expression in normal mammary epithelium, benign breast lesions, primary tumors, and metastatic foci.
- Confirmed findings using paired Northern blot analysis of RNA from normal and tumor tissues.
Main Results:
- The c-kit receptor was unexpectedly found in normal mammary epithelium.
- c-kit product was detected in 82% of benign breast lesions.
- In primary tumors, c-kit product was absent in 87% of cases, a phenotype maintained in metastases.
Conclusions:
- The c-kit receptor plays a role in mammary epithelium growth control.
- c-kit function appears impaired during malignant transformation and dedifferentiation of breast tissue.
- Loss of c-kit expression may be a marker of breast cancer progression.