Signaling and regulation of transcription factor nuclear factor-kappaB (NF-κB) has been an area of extensive research since its first discovery nearly three decades ago. Members of the NF-κB family have been reported to critically mediate a multitude of responses in normal cells. Therefore, it is not surprising that NF-κB function can go awry and result in pathological conditions including cancer. Despite its critical importance, the functional role of NF-κB has not received the same attention in cancers of all tissue types. In the case of cancer of the urinary bladder, which is the second most common urologic cancer, the involvement of NF-κB in the development of superficial or muscle invasive disease and during cancer recurrence is rudimentary at best. Nuclear expression of p65/RelA is seen in bladder cancer patients and has been found to negatively affect survival of patients with superficial and muscle invasive disease. Despite these observations, the exact mechanism of NF-κB upregulation and function remains unknown. Furthermore, the emergence of a tumor suppressive role for NF-κB in recent years suggests that the family may play the role of a double-edged sword in cancer, which remains unexplored in bladder cancer. The challenge now is to delineate the increasing complexity of this pathway in the development and progression of bladder cancer. Here, we review key aspects of the current knowledge of signaling and regulation by the NF-κB family focusing on its controversial role in cancer and highlight the importance of studying NF-κB in bladder cancer in particular.
Endocrine disrupting chemicals disrupt normal physiological function of endogenous hormones, their receptors, and signaling pathways of the endocrine system. Most endocrine disrupting chemicals exhibit estrogen/androgen agonistic and antagonistic activities that impinge upon hormone receptors and related pathways. Humans are exposed to endocrine disrupting chemicals through food, water and air, affecting the synthesis, release, transport, metabolism, binding, function and elimination of naturally occurring hormones. The urogenital organs function as sources of steroid hormones, are targeted end organs, and participate within systemic feedback loops within the endocrine system. The effects of endocrine disruptors can ultimately alter cellular homeostasis leading to a broad range of health effects, including malignancy. Human cancer is characterized by uncontrolled cell proliferation, mechanisms opposing cell-death, development of immortality, induction of angiogenesis, and promotion of invasion/metastasis. While hormonal malignancies of the male genitourinary organs are the second most common types of cancer, the molecular effects of endocrine disrupting chemicals in hormone-driven cancers has yet to be fully *
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