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Investigating Ras homolog gene family member C (RhoC) and Ki67 expression following external beam radiation therapy show increased RhoC expression in relapsing prostate cancer xenografts

Kristiansson, Amanda LU ; Ceberg, Crister LU orcid ; Bjartell, Anders LU ; Ceder, Jens LU and Timmermand, Oskar Vilhelmsson LU (2024) In Biochemical and Biophysical Research Communications 728.
Abstract

Ras homolog gene family member C (RhoC) is a GTPase involved in cell migration, implicated in epithelial-mesenchymal transition and treatment resistance and metastasis of cancer. For example, RhoC has been shown to be involved in resistance to radiation in cervical carcinoma. Here, the effect of X-ray irradiation on RhoC expression in prostate cancer (PCa) xenografts was investigated in both xenografts in regression and relapse. Male BALB/cAnNRj-Foxn1nu/nu mice were inoculated with 4–6 million LNCaP-FGC cells and established xenografts were irradiated with X-rays (200 kV, 1 Gymin-1), 5, 10 or 15 Gy using a Gulmay Medical X-ray system. Expression of RhoC and Ki67, a known proliferation marker, was investigated in... (More)

Ras homolog gene family member C (RhoC) is a GTPase involved in cell migration, implicated in epithelial-mesenchymal transition and treatment resistance and metastasis of cancer. For example, RhoC has been shown to be involved in resistance to radiation in cervical carcinoma. Here, the effect of X-ray irradiation on RhoC expression in prostate cancer (PCa) xenografts was investigated in both xenografts in regression and relapse. Male BALB/cAnNRj-Foxn1nu/nu mice were inoculated with 4–6 million LNCaP-FGC cells and established xenografts were irradiated with X-rays (200 kV, 1 Gymin-1), 5, 10 or 15 Gy using a Gulmay Medical X-ray system. Expression of RhoC and Ki67, a known proliferation marker, was investigated in xenografts, given 15 Gy, 7 days (midst response as measured by size) or 3 weeks (relapse) post irradiation. Staining was quantified using the Halo software (v2.3.2089.34) with the Indica Labs – cytonuclear v1.6 algorithm. RhoC and Ki67 staining was divided into weak, medium, and strong staining and the percentage of cells stained, single and dual staining, was quantified. The HALO software was further used to classify the tissue in each section so that analysis of RhoC and Ki67 expression in cancer cells, stroma and necrotic areas could be done separately. The results showed that RhoC expression in cancer and stroma cells was significantly higher in relapsed xenografts than in those in regression. This was not seen for Ki67 staining, where the percentage of stained cells were the same in regressing and relapsing tumors. RhoC could be a useful biomarker to confirm relapse following external beam radiation therapy.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
External beam radiation, Prostate cancer, Radioresistance, RhoC, Xenograft mouse model
in
Biochemical and Biophysical Research Communications
volume
728
article number
150324
publisher
Elsevier
external identifiers
  • pmid:38968772
  • scopus:85197303692
ISSN
0006-291X
DOI
10.1016/j.bbrc.2024.150324
language
English
LU publication?
yes
id
364311c0-c0ee-4e4f-88ea-0b002dc47d56
date added to LUP
2024-09-03 14:26:50
date last changed
2024-09-03 14:58:30
@article{364311c0-c0ee-4e4f-88ea-0b002dc47d56,
  abstract     = {{<p>Ras homolog gene family member C (RhoC) is a GTPase involved in cell migration, implicated in epithelial-mesenchymal transition and treatment resistance and metastasis of cancer. For example, RhoC has been shown to be involved in resistance to radiation in cervical carcinoma. Here, the effect of X-ray irradiation on RhoC expression in prostate cancer (PCa) xenografts was investigated in both xenografts in regression and relapse. Male BALB/cAnNRj-Foxn1<sup>nu/nu</sup> mice were inoculated with 4–6 million LNCaP-FGC cells and established xenografts were irradiated with X-rays (200 kV, 1 Gymin<sup>-1</sup>), 5, 10 or 15 Gy using a Gulmay Medical X-ray system. Expression of RhoC and Ki67, a known proliferation marker, was investigated in xenografts, given 15 Gy, 7 days (midst response as measured by size) or 3 weeks (relapse) post irradiation. Staining was quantified using the Halo software (v2.3.2089.34) with the Indica Labs – cytonuclear v1.6 algorithm. RhoC and Ki67 staining was divided into weak, medium, and strong staining and the percentage of cells stained, single and dual staining, was quantified. The HALO software was further used to classify the tissue in each section so that analysis of RhoC and Ki67 expression in cancer cells, stroma and necrotic areas could be done separately. The results showed that RhoC expression in cancer and stroma cells was significantly higher in relapsed xenografts than in those in regression. This was not seen for Ki67 staining, where the percentage of stained cells were the same in regressing and relapsing tumors. RhoC could be a useful biomarker to confirm relapse following external beam radiation therapy.</p>}},
  author       = {{Kristiansson, Amanda and Ceberg, Crister and Bjartell, Anders and Ceder, Jens and Timmermand, Oskar Vilhelmsson}},
  issn         = {{0006-291X}},
  keywords     = {{External beam radiation; Prostate cancer; Radioresistance; RhoC; Xenograft mouse model}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Investigating Ras homolog gene family member C (RhoC) and Ki67 expression following external beam radiation therapy show increased RhoC expression in relapsing prostate cancer xenografts}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2024.150324}},
  doi          = {{10.1016/j.bbrc.2024.150324}},
  volume       = {{728}},
  year         = {{2024}},
}