Project: Research project

Project Details


The experiments proposed in this application are designed to elucidate
the mechanisms by which transforming growth factor beta1 (TGFbeta1)
stimulates colony formation in soft agar. TGFbeta is unique in that
regard since it is the only supplement when added to serum containing
medium which consistently initiates and maintains soft agar colony
growth. Since the ability of normal anchorage-dependent cultures to grow
in an anchorage-independent manner is one of the best in correlates with
tumorigenicity, the identification of specific regulatory genes might
provide insights to the initial, and presumably rate limiting, events
controlling neoplastic growth. It is our contention that expression of a
unique program of genes, relative to that required for monolayer growth,
is initiated by TGFbeta1 for soft agar growth; transformation might
result from the constitutive or altered expression of these genes. Once
these genes have been activated, the normal cellular machinery needed for
cell division is operative. Moreover, inhibiting the expression of these
genes may reestablish many aspects of normal growth control. We will
test these hypotheses by 1) identifying unique cDNAs whose expression is
specifically modulated during TGFbeta1-stimulated suspension growth; 2)
determining whether a common set of genes are similarly expressed and
required in various transformed cell lines; and 3) characterizing the
cell cycle and growth factor regulated expression of specific proteins
encoded by the clones isolated in the previous aims. These studies will
not only increase our understanding of the events leading to
tumorigenicity, but hopefully suggest new targets for therapeutic
Effective start/end date4/1/933/31/97


  • Medicine(all)