[Dioxin-l] Inhibits Estrogen-Induced Breast Cancer Cell Proliferation

[Tony Tweedale]

New Protein Inhibits Estrogen-Induced Breast
Cancer Cell Proliferation


WASHINGTON, Dec 17 (Reuters Health) - MG132, an inhibitor of the
ubiquitin-proteasome pathway, inhibits the proliferation of breast cancer ce=
lls
and abolishes estrogen's growth-promoting effects on them, according to a
presentation at the annual meeting of the American Society of Cell Biology.

Dr. Benjamin S. Leung from the University of Minnesota, Minneapolis, and
associates cultured two hormone-dependent breast cancer cell lines (MCF-7
and CAMA-1) and investigated the effects of MG132 on cell cycle progression.

Administration of estrogen (1 nanomolar or 10 nanomolar) or tamoxifen (10
micromolar) to breast cancer cells increased cellular proliferation, as
evidenced by a greater number of cells in G0/G1 (66.58%, 67.22%, and
84.48%, respectively, compared with 59.09% for untreated cancer cells), Dr.
Leung reported.

"Adding 10 micromolar MG132 to the medium for 48 hours returned the
percentages to those seen in the untreated controls and reduced the
percentage of
control breast cancer cells in G0/G1." Dr. Leung said in an interview with
Reuters Health.

MG132 appears to work by arresting the cell cycle prior to the S phase, Dr.
Leung said, as evidenced by substantial increases in the percentages of cell=
s
remaining in G2/M.

"Taken together, these results provide the first evidence of the involvement=
 of
the ubiquitin-proteasome proteolytic pathway in estrogen-regulated
proliferation of breast cancer cells," Dr. Leung noted.

Dr. Leung suggested that MG132 "...certainly has therapeutic potential for
breast cancer. We still need to find a way to target the MG132 to breast can=
cer
cells, because, as the name suggests, this pathway is ubiquitous. Its
interruption by MG132 would presumably affect any rapidly dividing cells."

In that sense, Dr. Leung said, MG132 would be similar to chemotherapeutic
drugs that have widespread effects in tissues that are constantly turning ov=
er.
He anticipated either being able to construct a targeted form of MG132 or us=
ing
it in its current form, with the attendant risks, as other anticancer
agents are
used.


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