TY - JOUR
T1 - Roles of p53, NF-κB and the androgen receptor in controlling NGAL expression in prostate cancer cell lines
AU - Chappell, William H.
AU - Candido, Saverio
AU - Abrams, Stephen L.
AU - Russo, Suzanne
AU - Ove, Roger
AU - Martelli, Alberto M.
AU - Cocco, Lucio
AU - Ramazzotti, Giulia
AU - Cervello, Melchiorre
AU - Montalto, Giuseppe
AU - Steelman, Linda S.
AU - Leng, Xiaohong
AU - Arlinghaus, Ralph B.
AU - Libra, Massimo
AU - McCubrey, James A.
N1 - Funding Information:
This research was supported in part by a grant from the Brody Brothers Foundation entitled, “Development of Non-invasive Biomarkers for Prostate, Brain, Head & Neck Cancer Patients”, Brody Brothers Foundation to JAM, SR and RO and an ECU research grant entitled, “Suppressing Prostate Cancer by Targeting NGAL” ECU grant number 112101668716 to JAM. We appreciate the assistance of Ms. Sue Ann Joyner in preparation of the IRB and the assistance of Ms. Jackie Unger and Ms. Toni Wittmann in obtaining the urine samples from the cancer patients.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/8
Y1 - 2018/8
N2 - Neutrophil gelatinase-associated lipocalin (NGAL a.k.a lipocalin 2, lnc2) is a secreted protein which can form a complex with matrix metalloproteinase-9 (MMP9). This MMP9/NGAL complex has been associated with metastasis. MMP9 and NGAL are detected in the urine of patients afflicted with many different types of cancer, including prostate cancer. The effects of p53, NF-κB and the androgen receptor (AR) on the expression of NGAL was examined in four prostate cancer cell lines. Prostate cancer cell lines that are AR negative and expressed either mutant or no p53 (DU145 and PC3) displayed higher levels of NGAL expression compared to the prostate cancer cell lines (LNCaP and 22Rv-1) which are AR positive and express wild type (WT) p53. Introduction of WT-p53 into the PC3 prostate cancer cell line, resulted in reduction of the levels of NGAL expression. Conversely, introduction of dominant negative (DN) p53 or a retroviral construct expressing NF-κB into LNCaP cells increased NGAL expression. NGAL expression had functional effects on the ability of the cells to form colonies in soft agar. Whereas suppression of WT-53 in LNCaP cells increased NGAL expression, the introduction of WT-p53 suppressed NGAL transcription activity in PC3 prostate cells which normally express high level of NGAL. NF-κB and p53 were determined to regulate NGAL expression by positive and negative mechanisms, respectively. Our data indicate that prostate cancer growth, progression and sensitivity to chemotherapeutic drugs are regulated in part by NGAL and may involve complex interactions between NGAL, MMP9, NF-κB and p53.
AB - Neutrophil gelatinase-associated lipocalin (NGAL a.k.a lipocalin 2, lnc2) is a secreted protein which can form a complex with matrix metalloproteinase-9 (MMP9). This MMP9/NGAL complex has been associated with metastasis. MMP9 and NGAL are detected in the urine of patients afflicted with many different types of cancer, including prostate cancer. The effects of p53, NF-κB and the androgen receptor (AR) on the expression of NGAL was examined in four prostate cancer cell lines. Prostate cancer cell lines that are AR negative and expressed either mutant or no p53 (DU145 and PC3) displayed higher levels of NGAL expression compared to the prostate cancer cell lines (LNCaP and 22Rv-1) which are AR positive and express wild type (WT) p53. Introduction of WT-p53 into the PC3 prostate cancer cell line, resulted in reduction of the levels of NGAL expression. Conversely, introduction of dominant negative (DN) p53 or a retroviral construct expressing NF-κB into LNCaP cells increased NGAL expression. NGAL expression had functional effects on the ability of the cells to form colonies in soft agar. Whereas suppression of WT-53 in LNCaP cells increased NGAL expression, the introduction of WT-p53 suppressed NGAL transcription activity in PC3 prostate cells which normally express high level of NGAL. NF-κB and p53 were determined to regulate NGAL expression by positive and negative mechanisms, respectively. Our data indicate that prostate cancer growth, progression and sensitivity to chemotherapeutic drugs are regulated in part by NGAL and may involve complex interactions between NGAL, MMP9, NF-κB and p53.
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U2 - 10.1016/j.jbior.2018.05.002
DO - 10.1016/j.jbior.2018.05.002
M3 - Article
C2 - 29861174
AN - SCOPUS:85048537068
SN - 2212-4926
VL - 69
SP - 43
EP - 62
JO - Advances in Biological Regulation
JF - Advances in Biological Regulation
ER -