J.
Cancer Mol. 4: 169-173, 2009
[Research
Paper]
Differential Regulation of Growth Factors and Matrix Metalloproteinase-1
by Estrogen, Progesterone, and Tamoxifen in Normal and Cancerous
Endometrial cells
Neena Philips, Michael Tahir, Jennifer
Stellatella, Kelly Stephan, Joshua Givant, Linda Zhou, Angelica Costa,
and May Taw
Biology, Fairleigh Dickinson University, Teaneck, NJ, USA [N. Philips,
M. Tahir, J. Givant, L. Zhou, A. Costa, M. Taw]; Biology/Chemistry,
Georgian Court University, Lakewood, NJ, USA [N. Philips, J. Stellatella,
K. Stephan]; Bergen County Academies, Hackensack, NJ, USA [J. Givant, L.
Zhou]
Abstract:
AIM:
The goal of this research was to determine the effects of estrogen,
progesterone, a combination of estrogen and progesterone, and tamoxifen
on normal or cancerous endometrial cells with regards to the expression
of transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF),
transforming growth factor-alpha (TGF-alpha), and matrix
metalloproteinase-1 (MMP-1); with implications to mechanisms by which
these hormones or anti-estrogen may facilitate or prevent cancer.
METHODS:
Normal and cancerous endometrial cells, respectively, were exposed to
estrogen, progesterone, a combination of estrogen and progesterone or
tamoxifen and examined for protein levels of TGF-alpha, TGF-beta, EGF
and MMP-1 by ELISA and for transcriptional regulation of MMP-1 by
transient transfection of MMP-1 promoter-reporter plasmid.
RESULTS:
Estrogen, progesterone and the combination of these hormones stimulated
the expression of TGF-alpha, TGF-beta, EGF and MMP-1 (transcriptionally)
in normal endometrial cells. In cancer cells, estrogen stimulated the
expression of TGF-alpha, TGF-beta, EGF and MMP-1 (transcriptionally) and
the combination of estrogen and progesterone further stimulated the
expression of these proteins, whereas progesterone did not have
significant effects. Tamoxifen inhibited MMP-1 expression
transcriptionally in normal and cancer cells, though to a greater extent
in normal cells, without significantly altering the expression of growth
factors.
CONCLUSION:
Estrogen and progesterone similarly stimulate the expression of growth
factors and MMP-1 in normal cells whereas progesterone potentiates the
effects of estrogen in cancer cells. It suggests that these hormones
are detrimental to normal cells as hormone replacement therapy, and
facilitate tumorigenesis especially in combination. However, tamoxifen
is beneficial to endometrial cells via the inhibition of MMP-1
expression.
(Keywords:
estrogen; progesterone; tamoxifen; hormone replacement therapy;
endometrial cells)
Received
8/14/08; Revised 11/16/08; Accepted 11/20/08.
1Correspondence:
Dr. Neena Philips, Biology, Fairleigh Dickinson University, 1000 River
Road H-DH4-03, Teaneck, NJ 07666, USA. Phone: 1-201-6926494. E-mail:
neenaphilips@optonline.net (or
nphilips@fdu.edu)
2Abbreviations:
MMP, matrix metalloproteinase; TGF-beta, transforming growth
factor-beta; EGF, epidermal growth factor; TGF-alpha, transforming
growth factor-alpha; CAT, chloramphenicol acetyltransferase.
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