Prostate cancer is one of the leading causes of death among men in the United States, and acquisition of hormone resistance (androgen independence) by cancer cells is a fatal event during the natural history of prostate cancer. Obesity is another serious health problem and has been shown to be associated with prostate cancer. However, little is known about the molecular basis of this association. Here we show that factor(s) secreted from adipocytes stimulate prostate cancer cell proliferation. Leptin is one of the major adipose cytokines, and it controls body weight homeostasis through food intake and energy expenditure. We identify leptin as a novel growth factor in androgen-independent prostate cancer cell growth. Strikingly, leptin stimulates cell proliferation specifically in androgen-independent DU145 and PC-3 prostate cancer cells but not in androgen-dependent LNCaP-FGC cells, although both cell types express functional leptin receptor isoforms. c-Jun NH 2 -terminal kinase (JNK) has been shown recently to play a crucial role in obesity and insulin resistance. Intriguingly, leptin induces JNK activation in androgen-independent prostate cancer cells, and the pharmacological inhibition of JNK blocked the leptin stimulation of androgenindependent prostate cancer cell proliferation. This suggests that JNK activation is required for leptin-mediated, androgen-independent prostate cancer cell proliferation. Furthermore, other cytokines produced by adipocytes and critical for body weight homeostasis cooperate with leptin in androgen-independent prostate cancer cell proliferation: interleukin-6 and insulin-like growth factor I demonstrate additive and synergistic effects on the leptin stimulation of androgen-independent prostate cancer cell proliferation, respectively. Therefore, adipose cytokines, as well as JNK, are key mediators between obesity and hormone-resistant prostate cancer and could be therapeutic targets.Prostate cancer is one of the leading causes of death among men in the United States. The disease is characterized by a prolonged natural history. Despite its relatively slow growth, a number of patients have persistent and/or recurrent disease. Initial treatment for many patients with recurrent disease is hormonal therapy to remove or decrease serum androgen as a potential growth stimulant for the prostate cancer. Although this approach is initially effective in the majority of patients, ultimately the disease becomes resistant to the loss of hormones, returns, and in many cases, culminates in the death of the patient. Thus, it is desired to develop effective therapies and preventives for hormone-resistant (androgen-independent) prostate cancer.Several lines of evidence indicate that obesity is a risk factor for prostate cancer. In particular, obesity is associated with clinical features characteristic of accelerated progression of prostate cancer: high mortality (1), prostatectomy at a younger age with high grade and more pathologically advanced cancer (2), and tendency for progression of stage B1-D1 ...

For the elucidation of the phylogenetic position of insectivora in eutheria, we have sequenced the cytochrome c oxidase subunit II (COII) gene of mitochondria for three insectivoran species [musk screw (Suncus murinus), shrew mole (Urotrichus talpoides), Japanese mole (Mogera wogura)] and analyzed these amino acid sequences with neighbor-joining (NJ) method and maximum likelihood (ML) method. NJ analysis shows polyphyly of Insectivora and Chiroptera. Assuming that each of Primates, Ferungulata, Chiroptera, Insectivora and Rodentia is a monophyletic group, ML analysis suggests that Chiroptera is a sister group of Insectivora and that Ferungulata is the closest outgroup to the (Insectivora and Chiroptera) clade.

Toky0106-856~Japan ABSTRACT-We sequenced the mitochondrial cytochrome b, 12S rRNA and 16S rRNA genes from three insectivoran species (Japanese mole, shrew mole and musk shrew) and one chiropteran species(Japanese pipistrelles) and the cytochrome c oxidase subunit II (Call) gene from a chiropteran species. The phylogenetic relationship of core Insectivora or Eulipotyphla among major Eutherian orders was examined for these genes. A total evaluation of the maximum likelihood analyses of the four genes suggests that Chiroptera is the closest to Eulipotyphla among 4 eutherian groups (Primates, Eulipotyphla, Fereuungulata, Rodentia).