Accession Number : ADA328870
Title : Programmed Cell Death Pathways in Tumor Initiation and Progression
Descriptive Note : Annual rept. 16 Sep 95-15 Sep 96
Corporate Author : FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
Personal Author(s) : Hockenbery, David M.
PDF Url : ADA328870
Report Date : OCT 1996
Pagination or Media Count : 14
Abstract : The effects of cellular apoptotic regulators on tumor initiation and progression are difficult to predict, as oncogenes may have either anti-apoptotic (bcl-2) and pro-apoptotic (c-myc) effects. Anti-apoptotic genes may promote tumor growth by rescuing cells susceptible to apoptosis, due to DNA damage, for example. Pro-apoptotic genes, on the other hand, might increase DNA damage as a substrate for genetic instability. We tested the ability of transgenic bcl-2 to interact with DMBA in the formation of murine mammary tumors. A modest increase in tumor incidence (73% vs 63%) was observed in DMBA-treated transgenic vs control female mice. We have examined mammary tumors from transgenic mice for apoptosis using the in situ TUNEL assay. Unexpectedly, apoptotic cells were present at relatively high levels, compared to normal breast tissue. Staining of serial sections with a monoclonal antibody to human Bcl-2 showed scattered areas of absent Bcl-2 expression, corresponding to TUNEL-positive cells. Finally, apoptotic indices in tumors from transgenic and control animals were comparable. Apoptosis is often associated with increased oxidative stress, a potential cause of DNA damage. An association between apoptosis, ROS, and genetic instability may explain the apparent retention of apoptotic programs in experimental and human tumors.
Descriptors : *NEOPLASMS, *CELLS(BIOLOGY), *GENETICS, *BREAST CANCER, TISSUES(BIOLOGY), HUMANS, STRESS(PHYSIOLOGY), DEOXYRIBONUCLEIC ACIDS, OXIDATION, MICE, DEATH, INSTABILITY, MAMMARY GLANDS, GROWTH(PHYSIOLOGY).
Subject Categories : Biochemistry
Genetic Engineering and Molecular Biology
Medicine and Medical Research
Distribution Statement : APPROVED FOR PUBLIC RELEASE