| Lung cancer
is the leading cause of cancer deaths for men
and women. The higher frequency of lung adenocarcinoma
in women than in men, in both smokers and non-smokers,
suggests that gender-dependent factors are part
of the causes of lung cancer. The long-term goal
of the proposed research is to determine the mechanism(s)
responsible for this gender bias for lung adenocarcinoma
in women.
The action of female hormones, estrogens, is
mediated by proteins called estrogen receptors
(ER) inside cells. Mucins are large proteins found
on cell surfaces that sense the environment outside
the cell and transmit signals about the environment
to the inside of the cell. Our proposal is based
on three findings. Recently one of these mucins,
called MUC1, was shown to bind to ER and to increase
the activity of ER. Second, a report published
this year by our collaborators found that although
lung cancer cells from men and women both contain
the same amount of ER, only in lung cancer cells
from women does exposure to estrogen stimulate
the cells to grow. Because uncontrolled growth
is a characteristic of cancer cells, these latter
results suggested that ER may be involved in the
gender bias for lung adenocarcinoma. Third, our
laboratory has found that there is a difference
in the frequency of two forms of MUC1 in lung
carcinoma cells from women as compared to cells
from men.
We propose that those different frequencies of
MUC1 forms, if confirmed by testing a larger number
of tumors, may be useful for predicting which
persons may be more or less susceptible to developing
lung adenocarcinoma. We also propose to characterize
the relationship between ER and MUC1 in order
to determine if the interaction of these two key
proteins may be involved in the gender bias for
lung adenocarcinoma in women.
|
