Publication: Modeling human breast cancer metastasis in mice: maspin as a paradigm
Authors
Shi, H.Y. ; Zhang, W. ; Liang, R. ; Kittrell, F. ; Templeton, N.S. ; Medina, D. ; Zhang, M.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Breast cancer is the most common cancer
detected in women, accounting for nearly one out of
every three cancers diagnosed in the United States. Most
cancer patients do not die from the primary tumor but
die due to metastasis. Therefore, the study of metastasis
is of most importance both to the clinician and patient.
In the past, animal models have been used in breast
cancer research and mammary gland biology. Our group
has also established several animal models to address the
function of a novel tumor suppressor gene maspin in
breast tumor progression. Maspin was initially isolated
from normal mammary epithelial cells. Its expression
was down regulated in breast tumors. To test the
protective role of maspin overexpression in mammary
tumor progression, we crossed maspin overexpression
transgenic mice (WAP-maspin) with a strain of
oncogenic WAP-SV40 T antigen mice. The bitransgenic
mice had reduced tumor growth rate and metastasis.
Maspin overexpression increased the rate of apoptosis of
both preneoplastic and carcinomatous mammary
epithelial cells. Maspin reduced tumor growth through a
combination of reduced angiogenesis and increased
apoptosis. In a separate animal experiment, maspin
overexpressing mammary tumor cells (TM40D) were
implanted into the fat pad of syngeneic mice. TM40D
tumor cells were very invasive and metastatic. However,
both primary tumor growth and metastasis were
significantly blocked in TM40D cells that overexpress maspin as a consequence of plasmid or retrovirus
infection. These evidences demonstrate that maspin
function to inhibit primary tumor growth as well as
invasion and metastasis. Elucidating the molecular
mechanism of maspin action will shed light on our
understanding of breast cancer invasion and metastasis.
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