The role of tgf- β in breast cancer

Breast cancer as most common cancer among woman is the second leading cause of cancer mortality in the woman worldwide. Annually, million and half woman are diagnosed with breast cancer and 502,000 cases die because of the disease. It is estimated the percentage of woman with breast cancer in 2020 to amount over 29% in the developed and 37% in the developing countries. Cytokines and growth factors, including the Transforming Growth Factor –β (TGF-β) superfamily, have important roles in initiation and progression of breast cancer. In normal breast tissue and even during the early stages of breast cancer initiation, the TGF-β signaling pathway function as a tumor suppressor via suppressing proliferation, while promoting differentiation and apoptosis. As cancer progresses, tumor cells becomeresistant to TGF-β mediated growth inhibition, and TGF-β promotes tumor progression and metastasis, likely in part through its promotion of an epithelial-to-mesenchymal transition(EMT). TGF- β which have three isoforms in mammalian (β1, β2and β3), inhibits proliferation in the most human breast cancer cell lines. There some reports that show growth-inhibitory antiestrogens can increase the production of TGF-β1 in hormonally responsive cell line, while estradiol and norethindrone can inhibit the expression of TGF-β 2 and β3. Recently, some developmental homeotic transcription factors such as, Six1, were identified that act as an important mediator of breast cancer progression and metastasis. Upregulation of TGF-β signaling increases Six1 levels which consequently induce an epithelial-mesenchymal transition (EMT). Overall, this phenomena cuse an increase in the tumor- initiating cell (TIC) characteristics and induction of late stage metastasis. Another transcription factor is Annexin A1(Anx A1) which belongs to the family of calcium/phospholipid – binding and actin regulatory proteins. This protein regulates TGF-β signaling and promotes that. There is a significant correlation between mip-106b expression and both six 1 and activated TGF-β signaling in human breast cancer tissues. The third transcription factor in this area is Fibulin-3 that inhibits TGF-β pathway in the breast cancer microenvironment. Fibulin -3 interacts with the type 1 TGF-β receptor (TβR1), and its expression decreases during breast cancer progression, then levels of fibulin -3 correlates with poorer prognosis. TGF-β inhibits growth of epithelial cell, therefore carcinoma cells are often defective in TGF-β responses. The role of TGF-β in metastasis seems to mediate by effect on the surrounding normal tissue

کلیدواژه ها:

Breast Cancer ، Cancer Prevention ، Gene and Cancer ، Cell and Cancer ، Cancer Genetics