Progression of PDMT is accompanied by lack of Fas and intense expression of Bcl-2 and PKC-epsilon.
Recent study has demonstrated the development of pregnancy-dependent mammary tumors (PDMTs) in GR/A mice during pregnancy and their regression by apoptotic cell death after parturition. In the present study, we examined the molecular machinery of PDMTs before and after parturition and in progression. The death associated-cell surface molecule Fas was expressed only when apoptosis occurred, and no expression could be determined after progression. Interestingly, death suppressor Bcl-2 showed down-regulation when apoptosis occurred, and intense expression after progression. Examination of the possible involvement of PKC isozymes showed that only PKC-epsilon showed drastic changes in expression: expression was not detected in normal mammary gland cells and PDMTs, but was instead seen only when PDMTs progressed to malignant tumors. On the basis of these results, we suggest that PDMT-regression is due to Fas-mediated apoptosis, and that lack of Fas, persistent expression of Bcl-2, and new expression of PKC-epsilon are essential events for tumor progression.
Suzuki
A
A
Daiichi Pharmaceutical Co., Ltd, Drug Safety Research Laboratory, Tokyo R&D Center, Edogawa-ku, Japan.
Goto
Y
Y
Iguchi
T
T
D000818:Animals; D015536:Down-Regulation; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic; D011493:Protein Kinase C / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D011493:Protein Kinase C