The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.
Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostate-specific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.
Yamamoto-Ishikawa
Kaori
K
Department of Urology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Suzuki
Hiroyoshi
H
Nezu
Masahiko
M
Kamiya
Naoto
N
Imamoto
Takashi
T
Komiya
Akira
A
Sogawa
Kazuyuki
K
Tomonaga
Takeshi
T
Nomura
Fumio
F
Ichikawa
Tomohiko
T
D000368:Aged; D000595:Amino Acid Sequence; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D053302:Apolipoprotein C-I / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D015153:Blotting, Western; D002460:Cell Line; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D040081:Protein Array Analysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
C505803:APOC1 protein, human; D018931:Antineoplastic Agents, Hormonal; D053302:Apolipoprotein C-I