AIMChromosome 13 is one of the most frequently altered chromosomes in prostate cancer. The present study was undertaken to examine the role of human chromosome 13 in the progression of prostate cancer.

METHODSHuman chromosome 13 was introduced into highly metastatic rat prostate cancer cells via microcell-mediated chromosome transfer.

RESULTSMicrocell hybrid clones containing human chromosome 13 showed suppression of metastasis to the lung without any suppression of tumorigenicity, except for one clone, which contained the smallest sized human chromosome 13 and did not show any suppression on lung metastasis. Expression of two known tumor suppressor genes, BRCA2 and RB1, which map to chromosome 13, was examined by reverse transcription- polymerase chain reaction analysis. BRCA2 was expressed only in the metastasis-suppressed microcell-hybrid clones, whereas RB1 was expressed in all clones.

CONCLUSIONHuman chromosome 13 contains metastasis suppressor gene(s) for prostate cancer derived from rat. Furthermore, the RB1 gene is unlikely to be involved in the suppression of metastasis evident in this system.

Animals ; Animals, Genetically Modified ; Cell Division ; genetics ; Chromosome Aberrations ; Chromosome Mapping ; Chromosomes, Human, Pair 13 ; Disease Progression ; Genetic Markers ; Humans ; In Situ Hybridization, Fluorescence ; Kinetics ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms ; genetics ; pathology ; prevention & control ; Rats ; genetics

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml^-1), intermediate (100-999 ng ml^-1), and high (≥1000 ng ml^-1). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.
Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Disease Progression ; Humans ; Male ; Middle Aged ; Prognosis ; Progression-Free Survival ; Prostate-Specific Antigen/blood* ; Prostatic Neoplasms/mortality* ; Treatment Outcome