In our study, active Stat5 distinguishes breast cancer patients with favorable prognosis, and may be a useful marker for selection of more individualized treatment, especially in localized disease. These findings require confirmation in a large prospective study.
There are currently no effective therapies for metastatic prostate cancer because the molecular mechanisms that underlie the metastatic spread of primary prostate cancer are unclear. Transcription factor Stat3 is constitutively active in malignant prostate epithelium, and its activation is associated with high histological grade and advanced cancer stage. Progression of prostate cancer to metastatic disease is one of the key problems in the clinical management of prostate cancer.1 This is because there are currently no effective therapies for metastatic prostate cancer, and metastatic prostate cancer is the lethal form of the disease. Identification of the molecular changes that lead to formation of distant metastasis is critical for improvement of therapeutic interventions for metastatic prostate cancer and for development of strategies to prevent primary prostate cancer from metastasizing.Transcription factor Stat3 has been implicated in the promotion of growth and progression of prostate cancer. Stat3, which is both a cytoplasmic signaling molecule and a nuclear transcription factor, belongs to the sevenmember Stat gene family of transcription factors.2 Stat3 becomes active by phosphorylation of a specific tyrosine residue in the carboxy-terminal domain by a tyrosine kinase (pY705).3 Activation of Stat3 is supplemented by phosphorylation of a specific serine residue (S727).4 After phosphorylation, Stat3 homodimerizes and translocates to the nucleus where it binds to specific Stat3 response elements of target gene promoters to regulate transcription.3 Transcription factor Stat3 is constitutively active in clinical human prostate cancer, 5-9 and activation of Stat3 has been associated with advanced stage of prostate cancer. 5,9 Moreover, several reports implicate Stat3 in promotion of prostate cancer cell proliferation and inhibition of apoptosis. 5,10,11
Prolactin is widely expressed in different tissues, and it is presumed to have both local and systemic actions. In males it is known to influence reproductive functions but the significance and mechanisms of prolactin action in male accessory reproductive tissues are poorly understood. Here we show that prolactin acts as a direct growth and differentiation factor for human prostate, as measured by changes in DNA synthesis and epithelial morphology of organ cultures.
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