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Soluble endoglin inhibits breast cancer cell proliferation
Author(s) -
Gingery Anne,
Nelson Adam M,
Soldner Emma L B,
Gilbert Jeffrey S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.816.4
Subject(s) - protein kinase b , breast cancer , pi3k/akt/mtor pathway , mapk/erk pathway , estrogen receptor , cancer research , cell growth , cancer , medicine , endoglin , estrogen , cancer cell , endocrinology , signal transduction , chemistry , biology , microbiology and biotechnology , biochemistry , stem cell , cd34
While recent studies indicate preeclampsia may be associated with reduced incidence of breast cancer, the exact mechanisms underlying this observation remain unknown. Soluble endoglin (sEng) is one of the factors increased due to placental ischemia in preeclampsia and may play a role in reduced incidence of breast cancer by altering TGFβ signaling. Previously we have shown that serum from our rat model of preeclampsia inhibits growth of breast cancer cells independent of estrogen receptor status. We hypothesized that sEng inhibits proliferation of breast cancer cells via MAPK and PI3K/Akt pathways. We examined the effects of sEng on MCF‐7 and LCC9 cells in vitro . MCF‐7 cells are estrogen sensitive, while LCC9 are non‐responsive to estrogen. sEng treatment (20 ng/mL) reduced proliferation of MCF‐7 (65.6% ‐ 24h) and LCC9 (68.2% ‐ 24h) breast cancer cells. Phospho‐Akt (47, 57, 76 %) and phosph‐Erk1/2 (28, 44, 57 %) activation was reduced in MCF‐7 cells at 5, 10 and 30 minutes post‐treatment with sEng. Total Akt and MEK protein levels remained constant, whereas total Erk protein levels decreased within 10 minutes of treatment with sEng. Taken together sEng may act by attenuating TGFβ signaling thereby inhibiting proliferation of MCF‐7 breast cancer cells through the Akt and Erk signaling pathways. The present data are a step towards identifying cellular mechanisms that may be exploited to develop novel therapeutic regimens.