• Slaga, Thomas J (PI)
  • Digiovanni, John (PI)

Project: Research project

Project Details


This proposed program project contains three highly relevant and
interrelated projects by a number of independent investigators at the
Science Park - Research Division (S.P.R.D.) of the University of Texas M.D.
Anderson Cancer Center. The primary objective of this program project is
to establish the importance, in an integrated manner, of specific genes,
gene products and genetic changes during multistage carcinogenesis using
the mouse skin model. The overall approach will allow us to determine the
sequential occurrence of these alterations, how these interrelate to each
other during the induction of cancer and the functional significance of
these changes during the carcinogenic process. Specific goals of the
program project are as follows: i) to determine the role of two cellular
receptors i.e., the epidermal growth factor receptor (EGFr) and the
glucocorticoid receptor (GcR) during multistage skin carcinogenesis
(Projects 2 and 3); ii) to determine the role of both a positive
[transforming growth factor alpha (TGFalpha)] and negative (TGFbeta) growth
factor during multistage skin carcinogenesis (Project 3); iii) to determine
the role of specific chromosomal changes during the tumor progression stage
of multistage skin carcinogenesis (Project 1); and iv) to establish and
correlate phenotypic changes (histological, biochemical, and molecular) in
premalignant skin lesions with genetic events linked to tumor progression
(Projects 1, 2 and 3). The overall hypotheses to be tested in this program
project are i) that changes in the expression (mRNA, protein) or function
of specific genes and gene products, including: TGFalpha, TGFbeta, EGRr,
GcR, Ha-ras, c-Fos, and PKC are either causal or permissive for specific
stages of multistage carcinogenesis in the skin, and ii) that certain
phenotypic changes in premalignant skin lesions can be directly linked to
specific genetic events (i.e., chromosomal changes) which are causal for
their progression to malignant skin lesions.
Effective start/end date8/1/925/31/98


  • National Institutes of Health


  • Medicine(all)


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