Page 7 - Read Online
P. 7

Page 2 of 17                         Gabriele et al. J Cancer Metastasis Treat 2018;4:17  I  http://dx.doi.org/10.20517/2394-4722.2018.06

               Table 1. Main genes involved in prostate cancer
                Gene            Full name                             Function/references
                BRCA1  Breast cancer susceptibility  DNA repair [7]
                       protein type 1
                BRCA2  Breast cancer susceptibility  DNA repair [7]
                       protein type 2
                HPC1   Hereditary prostate cancer  Prostate cancer susceptibility ribonuclease L [8]
                VDR    Vitamin D receptor       Inhibition of cell growth, metastasis and angiogenesis; apoptosis modulation and cell
                                                differentiation [8]
                CD82   Cluster of differentiation 82  Metastasis suppressor attenuates the matrix adhesion [9]
                PTEN   Phosphatase and tensin homolog  Tumor suppressor and cell cycle regulation [9]
                mTOR   Mammalian target of rapamycin  Key signaling pathway linked to tumorigenesis and resistance to therapy [10]
                PSA    Prostate specific antigen  Dissolver of cervical mucus, allowing the entry of sperm in the uterus [11]
                BCL2   B-cell lymphoma 2        Pro-survival protein associated with the development of androgen-independent
                                                prostate cancer [12]
                MKI67  Antigen Ki-67            Nuclear protein involved cell proliferation [13]
                ERK-5  Mitogen-actvated protein kinase 7  Signaling processes of various receptor molecules. In response to extracellular signals,
                                                this kinase translocate to the nucleus, where it regulates gene expression and activates
                                                different transcription factors [14]
                SP1    Transcription factor Sp1  Involved in many cellular processes, including cell differentiation, growth, apoptosis,
                                                immune responses, DNA damage, and chromatin remodeling [15]
                TPD52  Tumor protein 52         Unknown [16]


               prostate cancer tends to develop in men over the age of fifty . Rates of detection of prostate cancers vary
                                                                   [1]
               widely across the world, with South and East Asia detecting less frequently than in Europe and in the
               United States. Globally, it is the sixth leading cause of cancer-related death in men . More than 200,000
                                                                                       [2]
               new cases are estimated in the United States in 2013, with a mortality rates over per 10 cases. Moreover,
               there are different ways of classifying patients with prostate cancer: the tumor-node-metastases (TNM)
               classification of malignant tumors evaluates the extension of the tumor, the involvement of lymph nodes and
               the metastatic dissemination. The Gleason Grading system is additionally used to evaluate the prognosis of
               men with prostate cancer. A Gleason score is given to prostate cancer based upon its microscopic appearance:
               cancers with a higher Gleason score are more aggressive and have a worse prognosis .
                                                                                      [3,4]

               Many factors, including genetics and diet, have been implicated in the development of this cancer. As
               suggested by association studies, genetic background can contribute to prostate cancer risk with family,
               race, and specific gene variants. Men who have a first-degree relative (brother or father) with prostate cancer
               have twice the risk of developing the cancer, and those with two first-degree relatives affected have a fivefold
               greater risk compared with men with no family history . Studies of twins in Scandinavia suggest that 40%
                                                              [5]
               of prostate cancer risk can be explained by inherited factors .
                                                                  [6]
               A summary of the different genes implicated in prostate cancer are highlighted in Table 1 [7-16] .



               METABOLISM AS A PRIVILEGED TARGET IN PROSTATE CANCER CELLS
               Different metabolic targets and sub-targets in prostate cancer
               The specific alterations in metabolic pathways observed in cancer cells confirm that tumors need unusual
               amounts of energy and biosynthetic precursors to survive and grow .
                                                                        [17]
               However, the unique intermediary metabolism in prostate cancer cells is substantially different from that
               found in other cancer cell types . In particular to satisfy the energy demand and to generate ATP, most
                                           [18]
               cancer cells are mainly derive energy from aerobic glycolysis . In androgen-dependent prostate cancer
                                                                     [19]
               cells, Warburg  has demonstrated that glucose does not play a major metabolic role because LNCaP
                            [19]
               cells, and androgen-sensitive human prostate adenocarcinoma cells  widely employed in in vitro prostate
                                                                         [20]
               cancer studies, can even grow in presence of low glucose concentrations . Therefore, the metabolic state
                                                                              [21]
               of prostate cancer cells is altered to satisfy the increased demand for energy that is required to support the
   2   3   4   5   6   7   8   9   10   11   12