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Novel protein kinases expressed in human breast cancer
W G Cance1, R J Craven, T M Weiner
1Department of Surgery, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill 27599.
Abstract:
The family of protein kinases includes many oncogenes and growth-factor receptors, as well as genes that are involved in cell-cycle regulation. We have identified protein kinases expressed in a human breast-cancer cell line, 600PEI, and a primary human breast carcinoma, using PCR cloning techniques based on consensus sequences in the kinase domain. Twenty-five different protein kinases were isolated, including 3 novel putative tyrosine kinases (designated TK1, TK2, and TK5), and 2 novel putative cell-cycle-associated serine/threonine kinases (designated STK1 and STK2). TK1 is a new member of the src family of kinases that is expressed predominantly in epithelial cells. TK2 is homologous to the receptor kinase, HEK, and TK5 appears to be another member of the JAK family of kinases. The novel serine/threonine kinases, designated STK1 and STK2, were homologous to the human cdc2 and the Aspergillus nimA genes. We subsequently analyzed the levels of expression of all of these protein kinases in a panel of human breast carcinomas, using PCR-based methods. This analysis revealed different expression profiles in different primary breast carcinomas and, therefore, may determine new molecular sub-sets of human breast cancer.
Insights
Researchers identified novel protein kinases in human breast cancer cells. These findings reveal distinct expression profiles that may define new molecular subtypes of breast cancer.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Protein kinases are crucial in cell signaling, cell-cycle regulation, and are implicated in oncogenesis.
- Dysregulation of protein kinases is a hallmark of many cancers, including breast cancer.
Purpose of the Study:
- To identify and characterize novel protein kinases expressed in human breast cancer.
- To investigate the expression profiles of these kinases in primary breast carcinomas to identify potential molecular subtypes.
Main Methods:
- Polymerase Chain Reaction (PCR) cloning techniques utilizing consensus sequences in the kinase domain.
- Analysis of protein kinase expression levels in a panel of human breast carcinomas using PCR-based methods.
Main Results:
- Twenty-five different protein kinases were isolated, including three novel tyrosine kinases (TK1, TK2, TK5) and two novel serine/threonine kinases (STK1, STK2).
- TK1 is a novel src family kinase predominantly expressed in epithelial cells.
- TK2 showed homology to the HEK receptor kinase, TK5 to the JAK family, and STK1/STK2 to cdc2 and nimA, respectively.
- Expression profiling revealed distinct kinase expression patterns across different primary breast carcinomas.
Conclusions:
- The identification of novel protein kinases provides new targets for understanding breast cancer.
- Differential expression profiles suggest the potential for defining new molecular subclasses of human breast cancer.
- This study lays the groundwork for targeted therapies based on specific kinase expression patterns.