Breast cancer is associated with loss of the c-kit oncogene product.
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.
Natali
P G
PG
Department of Immunology, Regina Elena Cancer Institute, Rome, Italy.
Nicotra
M R
MR
Sures
I
I
Mottolese
M
M
Botti
C
C
Ullrich
A
A
D015152:Blotting, Northern; D001940:Breast / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics*; D002403:Cathepsins / Q000378:metabolism; D004848:Epithelium / Q000502:physiology; D015870:Gene Expression; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011987:Receptors, Steroid / Q000378:metabolism
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011987:Receptors, Steroid; D019009:Proto-Oncogene Proteins c-kit; D002403:Cathepsins