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INVOLVMENT OF TGF-BETA AND PRB THE ACIDINDUCED GROWTH
ARREST OF HUMAN COLON CARCINOMA CELLS. Chanda Macias; Department of
Biochemistry, College of Medicine, Howard University, Washington,
DC.
Retinoid acid (RA) has been shown to inhibit proliferation and induce
differentiation in various cell types. The mechanism of retinoid action,
while not completely understood, is known to involve the regulation of
genes which control the inhibition of proliferation and the induction of
differentation. Our preliminary studies on the growth and differentation
of HT-29, human colon carcinoma cells in vitro demonstrated that 13-cis RA
caused a 20 to 70% inhibition of growth in a time-dependent manner with
maximum inhibition achieved after 96 hours of treatment.
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Retinoid Acid-Induced inhibition of proliferation of neoplastic cells has
been associated with the induction of transforming growth factor beta
(TGF-B) and the hypophosphorylation of the retinoblastoma protein (pRB).
However, the involvment of either TGF-B or pRB in the RA induced inhibition
of colon carcinoma cells remains to be determined. Therefore we will
determine whether the RA-induced inhibition of HT-29 proliferation is
associated with TGF-B expression. If TGF-B is up regulated, we will
ascertain the state of pRb phosphorylation to assess the involvment of the
TGF-B/pRb signaling mechanism.
McNair Alumni
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