Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer: Pathological implications in diagnosis

Sukwinder Kaur, Navneet Momi, Subhankar Chakraborty, David G. Wagner, Adam J. Horn, Subodh M Lele, Dan Theodorescu, Surinder Kumar Batra

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Material and Methods: Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. Results: MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p<0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). Conclusion: The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.

Original languageEnglish (US)
Article numbere92742
JournalPloS one
Volume9
Issue number3
DOIs
StatePublished - Mar 26 2014

Fingerprint

mucins
Mucins
Urinary Bladder Neoplasms
carcinoma
Cells
Tissue
Urothelium
Cell signaling
Glycosylation
Carcinoma
bladder
Biopsy
Cell membranes
Microarrays
Urinary Bladder
Monoclonal Antibodies
urinary bladder neoplasms
cell lines
Cell Line
resection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer : Pathological implications in diagnosis. / Kaur, Sukwinder; Momi, Navneet; Chakraborty, Subhankar; Wagner, David G.; Horn, Adam J.; Lele, Subodh M; Theodorescu, Dan; Batra, Surinder Kumar.

In: PloS one, Vol. 9, No. 3, e92742, 26.03.2014.

Research output: Contribution to journalArticle

Kaur, Sukwinder ; Momi, Navneet ; Chakraborty, Subhankar ; Wagner, David G. ; Horn, Adam J. ; Lele, Subodh M ; Theodorescu, Dan ; Batra, Surinder Kumar. / Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer : Pathological implications in diagnosis. In: PloS one. 2014 ; Vol. 9, No. 3.
@article{05bb1483bf8142af95c18c69ae550154,
title = "Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer: Pathological implications in diagnosis",
abstract = "Purpose: Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Material and Methods: Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. Results: MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p<0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). Conclusion: The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.",
author = "Sukwinder Kaur and Navneet Momi and Subhankar Chakraborty and Wagner, {David G.} and Horn, {Adam J.} and Lele, {Subodh M} and Dan Theodorescu and Batra, {Surinder Kumar}",
year = "2014",
month = "3",
day = "26",
doi = "10.1371/journal.pone.0092742",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer

T2 - Pathological implications in diagnosis

AU - Kaur, Sukwinder

AU - Momi, Navneet

AU - Chakraborty, Subhankar

AU - Wagner, David G.

AU - Horn, Adam J.

AU - Lele, Subodh M

AU - Theodorescu, Dan

AU - Batra, Surinder Kumar

PY - 2014/3/26

Y1 - 2014/3/26

N2 - Purpose: Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Material and Methods: Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. Results: MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p<0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). Conclusion: The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.

AB - Purpose: Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Material and Methods: Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. Results: MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p<0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). Conclusion: The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.

UR - http://www.scopus.com/inward/record.url?scp=84899989153&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899989153&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0092742

DO - 10.1371/journal.pone.0092742

M3 - Article

C2 - 24671186

AN - SCOPUS:84899989153

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e92742

ER -