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ABSTRACT:
G. Shyamala of Berkeley Lab has created a transgenic mouse
strain in which the native ratio of the A:B forms of progesterone
receptor (PR) has been altered by introduction of additional
"A" forms as transgene. PR belongs to the superfamily
of steroid receptors and mediates the action of progesterone.
The ratio of the two molecular forms, A and B, varies among
target tissues, and it is believed that their differential
expression and actions may be critical for appropriate cellular
responsiveness to progesterone. Almost all studies to date
have employed in vitro models — using either immortalized
or tumorigenic cell lines — to investigate the relative
activity of the A and B forms of PR. Only results from in
vivo models, such as Berkeley Lab's PR-A mice, can be extrapolated
to an understanding of normal developmental processes, human
polymorphisms related to uterine cancer, or the endocrine
basis of breast cancer and cancer of the female reproductive
tract. An in vivo model is also essential for screening a
variety of progestins and antiprogestins selected as potential
candidates for treatment of various clinical disorders, such
as hormone-dependent breast tumors. Further, Berkeley Lab's
PR-A transgenic mice can also be used to screen progestins
that can differentially affect the uterus and the breast in
post-menopausal women, for use in hormone replacement therapy.
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