Disclosed is a method of inhibiting neoplastic cellular proliferation and/or
transformation of mammalian cells, including cells of human origin, in vitro or
in vivo. The inventive method involves the use of a pituitary tumor transforming
gene carboxy-terminal peptide (PTTG-C), which has the ability to regulate endogenous
pituitary, tumor transforming gene (PTTG) expression and/or function in a dominant
negative manner. In some embodiments, the invention is directed to gene-based treatments
that deliver PTTG-C-related polynucleotides to mammalian cells, whether in vitro
or in vivo, to inhibit the endogenous expression of PTTG. Other embodiments are
directed to peptide-based treatments that deliver PTTG-C peptide molecules to the
cells, which inhibit endogenous PTTG expression and/or PTTG function. Additional
embodiments directed to a method of inhibiting tumor angiogenesis, in vivo, are
also disclosed. Also disclosed are compositions useful for inhibiting neoplastic
cellular proliferation and/or transformation and tumor angiogenesis, including
compositions comprising a PTTG carboxy-terminal peptide or comprising a chimeric
or fusion protein that contains a first PTTG carboxy-terminal peptide segment and
a second cellular uptake-enhancing and/or importation-competent peptide segment.
Also disclosed are compositions comprising a PTTG carboxy-terminal-related polynucleotide,
including compositions comprising expression vectors containing the PTTG-C-related
polynucleotides. Kits comprising the inventive compositions are also disclosed
for the treatment of neoplastic cellular proliferation in vitro or in vivo. Isolated
PTTG-C peptides and PTTG-C-related polynucleotides are also disclosed, as are anti-PTTG-C-specific antibodies.
