Protein Kinases in Mammary Gland Development and Carcinogenesis
Abstract
In this report, we present evidence that two novel kinases, Hunk (hormonally upregulated neu-tumor associated kinase) and Punc (pregnancy upregulated novel CaM kinase) isolated in a screen designed to identify protein kinases involved in mammary gland differentiation and carcinogenesis may be playing a role in both processes. Hunk and Punc are both developmentally regulated with Hunk levels highest early in pregnancy and Punc expression peaking late in pregnancy. In addition, their punctate spatial expression patterns suggest that Hunk and Punc may be markers for mammary epithelial cell subtypes. Consistent with their developmentally regulated expression patterns, we provide initial data suggesting that Hunk, in the context of an MMTV transgenic animal, affects normal differentiation of the mammary gland. Data also suggests that Hunk and Punc may be playing a role in carcinogenesis. Both kinases display an oncogene-restricted expression pattern with Punc expressed exclusively in tumor cell lines initiated by int-2 and c-myc and Hunk expression restricted to Neu and H-ras transformed cell lines. Investigation of kinase expression in a panel of human tumor cell lines and in primary human tumors reveals expression of Hunk and Punc in subsets of cell lines of different tumor types, including several breast cancers. Taken together, we hypothesize that Hunk and Punc may be kinases in signal transduction cascades involved in both the development and possibly the transformation of the mammary epithelium.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADB259038
Entities
People
- Lewis A Chodosh
Organizations
- University of Pennsylvania