Project Details
Description
This project is designed to characterize the potential for differentiation
therapy based on molecular mechanisms of differentiation promoters acting
on human colon carcinoma. Preliminary observations in a well-characterized
system of colonic carcinoma cell lines with diverse biological properties
(Brattain et al., 1984) and results obtained in their response to various
differentiation promoters, have led us to the hypothesis that the induction
of extracellular matrix (ECM) components is a critical step in the
differentiation process. Cellular ECM's individual ECM components and
combinations of ECM components will be assessed for their ability to induce
differentiation responses. Combinations of differentiation promoters, ECM
and individual components will be characterized for their ability to
enhance the differentiation of partially responsive or completely
unresponsive lines to individual differentiation promoting agents.
Differentiation and growth control have been closely linked to the
expression of autocrine growth factors. It is not known how ECM or ECM
components will affect the expression of these genes, but ECM has been
shown specifically to induce the expression of differentiated products such
as casein in cultured mammary cells. Expression of mRNA's for a
stimulatory autocrine factor (transforming growth factor-a) and an
inhibitory autocrine factor (transforming growth factor-B) as a function of
ECM induced differentiation will be characterized.
therapy based on molecular mechanisms of differentiation promoters acting
on human colon carcinoma. Preliminary observations in a well-characterized
system of colonic carcinoma cell lines with diverse biological properties
(Brattain et al., 1984) and results obtained in their response to various
differentiation promoters, have led us to the hypothesis that the induction
of extracellular matrix (ECM) components is a critical step in the
differentiation process. Cellular ECM's individual ECM components and
combinations of ECM components will be assessed for their ability to induce
differentiation responses. Combinations of differentiation promoters, ECM
and individual components will be characterized for their ability to
enhance the differentiation of partially responsive or completely
unresponsive lines to individual differentiation promoting agents.
Differentiation and growth control have been closely linked to the
expression of autocrine growth factors. It is not known how ECM or ECM
components will affect the expression of these genes, but ECM has been
shown specifically to induce the expression of differentiated products such
as casein in cultured mammary cells. Expression of mRNA's for a
stimulatory autocrine factor (transforming growth factor-a) and an
inhibitory autocrine factor (transforming growth factor-B) as a function of
ECM induced differentiation will be characterized.
| Status | Finished |
|---|---|
| Effective start/end date | 12/1/89 → 11/30/02 |
Funding
- National Institutes of Health: $139,416.00
- National Institutes of Health: $188,952.00
- National Institutes of Health: $231,019.00
- National Institutes of Health: $174,696.00
- National Institutes of Health: $210,494.00
- National Institutes of Health: $205,571.00
- National Institutes of Health: $113,164.00
ASJC
- Medicine(all)
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