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Cell-based evidence regarding the role of FSH in prostate cancer

Dizeyi, Nishtman LU ; Trzybulska, Dorota LU ; Al-Jebari, Yahia LU ; Huhtaniemi, Ilpo LU and Lundberg Giwercman, Yvonne LU (2019) In Urologic Oncology: Seminars and Original Investigations 37(4). p.1-290
Abstract

Introduction: Conversion of androgen-responsive prostate cancer (CaP) to castration-resistant CaP) is associated with an acceleration of the disease that often requires treatment modalities other than androgen deprivation therapy only. Recently, follicle-stimulating hormone (FSH) has been shown to play a role in CaP growth, and clinical data showed that high serum concentration of FSH in chemically castrated CaP patients was associated with a shorter time of progression to castration-resistant CaP. In this study, we sought to investigate if FSH could have direct effects on CaP cells, possibly through the androgen receptor and androgen receptor regulated genes, such as prostate-specific antigen (PSA). Materials and methods: The human CaP... (More)

Introduction: Conversion of androgen-responsive prostate cancer (CaP) to castration-resistant CaP) is associated with an acceleration of the disease that often requires treatment modalities other than androgen deprivation therapy only. Recently, follicle-stimulating hormone (FSH) has been shown to play a role in CaP growth, and clinical data showed that high serum concentration of FSH in chemically castrated CaP patients was associated with a shorter time of progression to castration-resistant CaP. In this study, we sought to investigate if FSH could have direct effects on CaP cells, possibly through the androgen receptor and androgen receptor regulated genes, such as prostate-specific antigen (PSA). Materials and methods: The human CaP cell lines PC-3, LNCaP and C4-2, and nonmalignant PNT1A cells, were utilized to investigate the effects of FSH. qPCR, Western blotting analysis, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymetoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium assays were performed in order to analyze the FSH effects. Results: The FSH receptor was present in all cell lines except PNT1A. FSH significantly increased PSA mRNA (P < 0.01) and protein (P < 0.03) levels in C4-2 cells in a dose-dependent manner. In LNCaP cells, FSH also increased PSA protein level, although to a lesser extent than in C4-2 cells, and the expression was reduced by the antiandrogen enzalutamide. In PC-3 cells, FSH was shown to increase their proliferation (P < 0.03) and β-catenin expression. Conclusion: These findings demonstrate that FSH may have a direct effect in CaP in an androgen-depleted environment. However, further research is needed to understand the significance of direct FSH action in the maintenance of CaP growth at the different phases of transition from androgen dependence to androgen independence.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Castration-resistant prostate cancer, Follicle-stimulating hormone receptor, Prostate-specific antigen, Signaling pathway
in
Urologic Oncology: Seminars and Original Investigations
volume
37
issue
4
pages
1 - 290
publisher
Elsevier
external identifiers
  • scopus:85059309540
  • pmid:30611646
ISSN
1078-1439
DOI
10.1016/j.urolonc.2018.12.011
language
English
LU publication?
yes
id
24f11e05-5b9c-4418-b747-ccd8f1eb496c
date added to LUP
2019-01-11 09:05:29
date last changed
2024-03-18 22:56:38
@article{24f11e05-5b9c-4418-b747-ccd8f1eb496c,
  abstract     = {{<p>Introduction: Conversion of androgen-responsive prostate cancer (CaP) to castration-resistant CaP) is associated with an acceleration of the disease that often requires treatment modalities other than androgen deprivation therapy only. Recently, follicle-stimulating hormone (FSH) has been shown to play a role in CaP growth, and clinical data showed that high serum concentration of FSH in chemically castrated CaP patients was associated with a shorter time of progression to castration-resistant CaP. In this study, we sought to investigate if FSH could have direct effects on CaP cells, possibly through the androgen receptor and androgen receptor regulated genes, such as prostate-specific antigen (PSA). Materials and methods: The human CaP cell lines PC-3, LNCaP and C4-2, and nonmalignant PNT1A cells, were utilized to investigate the effects of FSH. qPCR, Western blotting analysis, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymetoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium assays were performed in order to analyze the FSH effects. Results: The FSH receptor was present in all cell lines except PNT1A. FSH significantly increased PSA mRNA (P &lt; 0.01) and protein (P &lt; 0.03) levels in C4-2 cells in a dose-dependent manner. In LNCaP cells, FSH also increased PSA protein level, although to a lesser extent than in C4-2 cells, and the expression was reduced by the antiandrogen enzalutamide. In PC-3 cells, FSH was shown to increase their proliferation (P &lt; 0.03) and β-catenin expression. Conclusion: These findings demonstrate that FSH may have a direct effect in CaP in an androgen-depleted environment. However, further research is needed to understand the significance of direct FSH action in the maintenance of CaP growth at the different phases of transition from androgen dependence to androgen independence.</p>}},
  author       = {{Dizeyi, Nishtman and Trzybulska, Dorota and Al-Jebari, Yahia and Huhtaniemi, Ilpo and Lundberg Giwercman, Yvonne}},
  issn         = {{1078-1439}},
  keywords     = {{Castration-resistant prostate cancer; Follicle-stimulating hormone receptor; Prostate-specific antigen; Signaling pathway}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{4}},
  pages        = {{1--290}},
  publisher    = {{Elsevier}},
  series       = {{Urologic Oncology: Seminars and Original Investigations}},
  title        = {{Cell-based evidence regarding the role of FSH in prostate cancer}},
  url          = {{http://dx.doi.org/10.1016/j.urolonc.2018.12.011}},
  doi          = {{10.1016/j.urolonc.2018.12.011}},
  volume       = {{37}},
  year         = {{2019}},
}