Cyclin D1 protein expression and gene polymorphism in colorectal cancer

J A McKay, J J Douglas, V G Ross, S Curran, G I Murray, J Cassidy, H L McLeod, Aberdeen Colorectal Initiative

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular localization of which is often altered in human tumor cells. A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma. We have investigated both the expression of cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55% of tumors, and while the absence of cyclin D1 protein was not associated with outcome (p = 0.81), high levels of protein expression (>50% of tumor cells expressing cyclin D1) correlated with significantly shortened overall survival (p = 0.01). Using polymerase chain reaction restriction fragment length polymorphism analysis, we determined the frequency of each genotype and found that CCND1 genotype was not related to overall survival (p > 0.05). In addition, genotype was unrelated to the level of expression and localization of cyclin D1 protein, as well as other key G1/S checkpoint proteins (p21, p27, p53, retinoblastoma) and tumor proliferation markers (proliferating cell nuclear antigen). However, higher levels of p27, and to a lesser extent p21, were associated with reduced cytoplasmic cyclin D1 protein (p = 0.029 and p = 0.054, respectively). In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)77-81
Number of pages5
JournalInternational Journal of Cancer
Volume88
Publication statusPublished - 2000

Keywords

  • HUMAN BREAST-CANCER
  • SQUAMOUS-CELL CARCINOMA
  • RETINOBLASTOMA PROTEIN
  • DEPENDENT KINASES
  • PROGNOSIS
  • OVEREXPRESSION
  • AMPLIFICATION
  • INHIBITORS
  • PATHWAY
  • SIGNAL

Cite this

McKay, J. A., Douglas, J. J., Ross, V. G., Curran, S., Murray, G. I., Cassidy, J., ... Aberdeen Colorectal Initiative (2000). Cyclin D1 protein expression and gene polymorphism in colorectal cancer. International Journal of Cancer, 88, 77-81.

Cyclin D1 protein expression and gene polymorphism in colorectal cancer. / McKay, J A ; Douglas, J J ; Ross, V G ; Curran, S ; Murray, G I ; Cassidy, J ; McLeod, H L ; Aberdeen Colorectal Initiative.

In: International Journal of Cancer, Vol. 88, 2000, p. 77-81.

Research output: Contribution to journalArticle

McKay, JA, Douglas, JJ, Ross, VG, Curran, S, Murray, GI, Cassidy, J, McLeod, HL & Aberdeen Colorectal Initiative 2000, 'Cyclin D1 protein expression and gene polymorphism in colorectal cancer', International Journal of Cancer, vol. 88, pp. 77-81.
McKay JA, Douglas JJ, Ross VG, Curran S, Murray GI, Cassidy J et al. Cyclin D1 protein expression and gene polymorphism in colorectal cancer. International Journal of Cancer. 2000;88:77-81.
McKay, J A ; Douglas, J J ; Ross, V G ; Curran, S ; Murray, G I ; Cassidy, J ; McLeod, H L ; Aberdeen Colorectal Initiative. / Cyclin D1 protein expression and gene polymorphism in colorectal cancer. In: International Journal of Cancer. 2000 ; Vol. 88. pp. 77-81.
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abstract = "Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular localization of which is often altered in human tumor cells. A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma. We have investigated both the expression of cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55{\%} of tumors, and while the absence of cyclin D1 protein was not associated with outcome (p = 0.81), high levels of protein expression (>50{\%} of tumor cells expressing cyclin D1) correlated with significantly shortened overall survival (p = 0.01). Using polymerase chain reaction restriction fragment length polymorphism analysis, we determined the frequency of each genotype and found that CCND1 genotype was not related to overall survival (p > 0.05). In addition, genotype was unrelated to the level of expression and localization of cyclin D1 protein, as well as other key G1/S checkpoint proteins (p21, p27, p53, retinoblastoma) and tumor proliferation markers (proliferating cell nuclear antigen). However, higher levels of p27, and to a lesser extent p21, were associated with reduced cytoplasmic cyclin D1 protein (p = 0.029 and p = 0.054, respectively). In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival. (C) 2000 Wiley-Liss, Inc.",
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T1 - Cyclin D1 protein expression and gene polymorphism in colorectal cancer

AU - McKay, J A

AU - Douglas, J J

AU - Ross, V G

AU - Curran, S

AU - Murray, G I

AU - Cassidy, J

AU - McLeod, H L

AU - Aberdeen Colorectal Initiative

PY - 2000

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N2 - Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular localization of which is often altered in human tumor cells. A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma. We have investigated both the expression of cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55% of tumors, and while the absence of cyclin D1 protein was not associated with outcome (p = 0.81), high levels of protein expression (>50% of tumor cells expressing cyclin D1) correlated with significantly shortened overall survival (p = 0.01). Using polymerase chain reaction restriction fragment length polymorphism analysis, we determined the frequency of each genotype and found that CCND1 genotype was not related to overall survival (p > 0.05). In addition, genotype was unrelated to the level of expression and localization of cyclin D1 protein, as well as other key G1/S checkpoint proteins (p21, p27, p53, retinoblastoma) and tumor proliferation markers (proliferating cell nuclear antigen). However, higher levels of p27, and to a lesser extent p21, were associated with reduced cytoplasmic cyclin D1 protein (p = 0.029 and p = 0.054, respectively). In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival. (C) 2000 Wiley-Liss, Inc.

AB - Cyclin D1 is a key cell cycle regulatory protein, the expression and subcellular localization of which is often altered in human tumor cells. A common A/G single nucleotide polymorphism (A870G) in exon 4 of the cyclin D1 gene, CCND1, is associated with the presence of 2 distinct mRNA transcripts for this G1/S regulatory protein, and CCND1 genotype has been related to prognosis in lung cancer and head and neck carcinoma. We have investigated both the expression of cyclin D1 protein and the CCND1 A870G polymorphism in 100 colorectal cancer patients. Immunohistochemistry demonstrated cyclin D1 protein expression in 55% of tumors, and while the absence of cyclin D1 protein was not associated with outcome (p = 0.81), high levels of protein expression (>50% of tumor cells expressing cyclin D1) correlated with significantly shortened overall survival (p = 0.01). Using polymerase chain reaction restriction fragment length polymorphism analysis, we determined the frequency of each genotype and found that CCND1 genotype was not related to overall survival (p > 0.05). In addition, genotype was unrelated to the level of expression and localization of cyclin D1 protein, as well as other key G1/S checkpoint proteins (p21, p27, p53, retinoblastoma) and tumor proliferation markers (proliferating cell nuclear antigen). However, higher levels of p27, and to a lesser extent p21, were associated with reduced cytoplasmic cyclin D1 protein (p = 0.029 and p = 0.054, respectively). In conclusion, we have demonstrated that high levels of cyclin D1 protein expression are related to outcome in colorectal cancer; however, the CCND1 A870G polymorphism is unrelated to either cyclin D1 protein expression or patient survival. (C) 2000 Wiley-Liss, Inc.

KW - HUMAN BREAST-CANCER

KW - SQUAMOUS-CELL CARCINOMA

KW - RETINOBLASTOMA PROTEIN

KW - DEPENDENT KINASES

KW - PROGNOSIS

KW - OVEREXPRESSION

KW - AMPLIFICATION

KW - INHIBITORS

KW - PATHWAY

KW - SIGNAL

M3 - Article

VL - 88

SP - 77

EP - 81

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

ER -