In the case of DAZAP1, we show that it can promote splicing when binding to exon or introns

cancer growth. Although inhibition of ER is a successful approach for patients with ER-positive tumors, some patients become resistant to antiestrogen therapy after an initial response. Subsequent studies revealed that E2 could exert its activity through G protein coupled estrogen receptor. Marjon et al. provided the first in vivo evidence that GPER played a critical role in breast tumor growth and metastasis. Cao and colleagues showed that EPA and DHA could switch the effects of estrogen from pro-survival and proliferative to pro-apoptotic in human breast cancer cell lines. EPA and DHA promoted such pro-apoptotic action of estrogen by sensitizing the GPER1-cAMPPKA pathway and blunting the response of EGFR, Erk1/2, and AKT signaling. Based Author Manuscript Author Manuscript Author Manuscript Author Manuscript Curr Pharmacol Rep. Author manuscript; available in PMC 2016 October 01. Gu et al. Page 11 on the known functional interaction between the estrogen and PPAR receptors, Manni et al. tested the hypothesis that the combination of estrogen receptor antagonist tamoxifen with n-3 PUFAs would have a better antitumor effect than either agent alone. In a chemical carcinogen induced mammary carcinogenesis mouse model, they demonstrated that the combination of tamoxifen and n-3 PUFAs could inhibit tumor development and proliferation to a greater extent than the individual interventions. These results provide a positive indication of better efficacy of escalating n-3 PUFA biologic effects and the pro-apoptotic signaling of estrogen in breast cancer cells, also provide us with a new vision for the potential application of n-3 PUFAs combined with hormone therapy for breast cancer. The sex hormones are particularly important for adults to maintain healthy bones. Loss of hormone production or reduced levels may lead to bone loss. It has been reported that hormonal therapy for women with breast cancer can reduce bone density at a significant rate, at least double that of women during early menopause. For men receiving hormone therapy during prostate cancer treatment, a significant drop of hip bone mineral density occurs frequently, up to 9.6% bone loss in the first year post treatment. A recent study reported that lower risk of hip fracture was associated with higher red blood cell AA, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19854301 EPA and total n-3 PUFAs. More importantly, the incidence of hip fractures nearly doubled with the highest red blood cell n-6/n-3 ratio . A positive AEB-071 correlation between n-3 PUFA levels in erythrocytes and bone mass was also reported in postmenopausal Korean women with osteoporosis. In Fat-1 transgenic mice with high endogenous n-3 PUFA levels, there was no significant bone loss after ovariectomy, while there was substantial bone loss after ovariectomy in wild type mice. Endogenously produced n-3 PUFAs can attenuate ovariectomy-induced bone loss, probably by reducing adipogenesis of bone marrow and osteoclastogenesis. Among several potential mechanism whereby n-3 PUFAs may affect the bone, antiinflammation may be critical. Cytokines are key regulators controlling the ratio of osteoprotegerin and receptor activator of NFkB ligand in bones. RANKL ligand is expressed in osteoblasts, while RANKL receptor RANK is expressed on osteoclasts. RANKL binds to RANK on osteoclasts to activate the receptor and stimulate osteoclast formation, and to suppress osteoclast apoptosis. OPG is a glycoprotein expressed by and secreted from osteoblasts. OPG can function as an antagonist bloc