Mechanism of Altered Control of Proliferation by Cyclic Amp/Protein Kinase A During Mammary Tumor Progression.
Abstract
We examine the hypothesis that alterations in the regulation of growth by prolactin (PRL) and cAMP during mammary tumor progression are related to the ERK and JNK MAP kinase signaling pathways known to be affected by cAMP and pertussis toxin (PT)-sensitive G proteins. Mammary epithelial cells from normal mouse mammary glands were compared to pregnancy-dependent (PDT) and ovarian- independent (OlT) mouse mammary tumors in serum-free, collagen gel cell culture. Inhibition of the ERK pathway by the MEK inhibitor, PD 098059, showed that this signaling pathway is involved in PRL- regulated proliferation of normal mammary epithelial cells and PDT. cAMP-stimulated proliferation of normal cells is also inhibited by PD as is the "autonomous" growth of OlT cells which occurs in the absence of added mitogens. However, cAMP inhibited ERK activity in normal cells and did not affect ERK activity in OlT or PDT indicating a lack of correspondence with cAMP stimulation (normal, PDT) and inhibition of growth (OlT). PRL was able to stimulate PT-sensitive ERK activity in normal cells only. JNK activity was not affected by cAMP or PT in normal cells and PDT. However, cAMP inhibited JNK activity in OlT suggesting a possible relationship to growth inhibition. These results suggest that the ERK cascade is only permissive for proliferation, and cAMP and hormones stimulate proliferation via other PT-sensitive pathways. The JNK pathway remains a candidate for a cAMP-sensitive proliferation associated pathway in OlT.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1998
- Accession Number
- ADA353827
Entities
People
- Walter Imagawa
Organizations
- University of Kansas Medical Center