Vincenzo Chiarugi/Marco Ruggieri: Role of three cancer <> p53, bcl2 and
c-myc on the apoptotic process. Tumori 82/3 (1996), ... Abstract:
"We review some of the most recent developments concerning three genes
involved in human cancer: p53, bcl2 and c-myc. Recent data have demonstrated
that the bcl2 gene protects tumor cells from apoptosis induced by a variety
of agents, including ionizing radiation, and is thus related to resistance
to DNA-damaging therapeutic agents. The p53 tumor suppressor gene, however,
has been related with growth arrest, apoptosis and thus with selective
sensitivity to the killing effects of ionizing radiation and DNA-damaging
drugs. This functional antagonism between the two genes was recently
substantiated in molecular terms by demonstration of reciprocal down-
regulation due to the presence of a p53-dependent transcription silencer
in the untranslated region of the bcl2 gene. Growth arrest in the G1 phase
of the cell cycle and induction of apoptosis are two distinct and dissectable
functions of p53: bcl2 is able to antagonize the induction of apoptosis
by p53, but not the growth arrest in G1. However, coexpression of bcl2 and
of the oncogene c-myc efficiently antagonizes effects on G1 arrest and
apoptosis, thus suggesting a cooperation between the two oncogenes. In
addition, c-myc disrupts other functions of genetic control in the early
G1 phase of the cell cycle including the expression of D1 cyclin. We believe
that knowledge of the functional/molecular interactions between these
three genes involved in human cancer is a fundamental prerequisite to improve
the knowledge on prognosis and to design innovative therapeutic approaches."

S. Chiou/L. Rao/E. White: Bcl-2 blocks p53-dependent apoptosis.
Mol. Cell Biol. 14 (1994), 2556-...

S. Cory/A. Harris/A. Strasser: Insights from transgenic mice regarding
the role of bcl-2 in normal and neoplastic lymphoid cells.
Phil. Trans. Royal Soc. London B Biol. Sci. 345 (1994), 289-...

R. Craig: The bcl-2 gene family. Sem. Cancer Biol. 6 (1995), 35-...

A. Fanidi/E. Harrington/G. Evan: Cooperative interaction between c-myc
and bcl2 proto-oncogenes. Nature 359 (1992), 554-556.

M. Fernandez-Sarabia/J. Bischoff: Bcl-2 associates with the ras-related
protein R-ras p23. Nature 366 (1993), 274-...

M. Hengartner/H. Horvitz: C-elegans cell survival gene ced-9 encodes a
functional homolog of the mammalian proto-oncogene bcl-2.
Cell 76 (1994), 665-...

D. Hockenbery: bcl-2 in cancer, development and apoptosis.
J. Cell Sci. Suppl. 18 (1994), 51-...

S. Kamada a.o.: Bcl-2 deficiency in mice leads to pleotropic abnormalities -
accelerated lymphoid cell death in the thymus and spleen, polycystic
kidney, hair hypopigmentation, and distorted small intestines.
Cancer Res. 55 (1995), 354-...

S. Korsmeyer a.o.: Bcl-2/Bax - a rheostat that regulates an anti-oxidant
pathway and cell death. Sem. Cancer Biol. 4 (1993), 327-...

N. Motoyama a.o.: Massive cell death of immature hematopoietic
cells and neurons in Bcl-x-deficient mice. Science 267 (1995), 1506-...

L. Rao a.o.: The adenovirus E1A proteins induce apoptosis, which is
inhibited by the E1B 19-kDa and Bcl-2 proteins.
Proc. Nat. Ac. Sci. USA 89 (1992), 9974-...

A. Strasser a.o.: Novel primitive lymphoid tumours induced in transgenic
mice by cooperation between myc and bcl2. Nature 348 (1990), 332-...

A. Strasser a.o.: Enforced BCL2 expression in B-lymphoid cells prolongs
antibody responses and elicits autoimmune disease.
Proc. Nat. Ac. Sci. USA 88 (1991), 8661-...

Y. Tsujimoto a.o.: Cloning of the chromosome breakpoint of neoplastic
B-cells with t(14:18) chromosome translocation. Science 226 (1984), 1097-...

H. Wang a.o.: Apoptosis regulation by interaction of Bcl-2 protein
and Raf-1 kinase. Oncogene 9 (1994), 2751-...