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Growth dysregulation and p53 accumulation in human primary colorectal cancer

Lookup NU author(s): Dr Ian Brotherick, Dr Brian Shenton, Ronald Wilson, Professor Frederick Campbell

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Abstract

p53 accumulation is common in colorectal cancer, but effects on growth homeostasis are unclear. In this study, DNA content, cell cycle phase fractions and DNA strand-breaks consistent with apoptosis were assessed by flow cytometry in 42 fresh primary colorectal tumours and matched normal mucosa, p53 accumulation was assessed in 37 fixed tumour sections, by immunohistochemistry. In normal mucosa, 10.3 ± 6.6% (mean ± s.d.) cells were in DNA synthesis phase while 28.7 ± 17.9% showed apoptosis. A relationship suggestive of growth homeostasis, was observed between these parameters (r = 0.8; P < 0.05). In cancers, a greater number of cells were in DNA synthesis phase (15.6 ± 12.9% tumour vs mucosa 10.3 ± 6.6%; P < 0.02) while fewer showed apoptosis than normal mucosa (18.5 ± 17.0% tumour vs mucosa 28.7 ± 17.9%; P < 0.01). DNA synthesis and apoptosis tractions were unrelated in cancers, suggesting growth dysequilibrium. p53 accumulation was detected in 59% (22/37) tumours and was associated with reduced apoptosis compared to p53-negative tumours or mucosa (14.8 ± 15% p53 accumulation vs 26.3 ± 18% p53-negative; P < 0.05; vs 28.7 ± 17.9% mucosa; P < 0.05), p53 accumulation was unrelated to DNA synthesis phase fractions. p53 accumulation is accompanied by reduced apoptosis which may accentuate growth dysequilibrium in colorectal cancer.

Publication metadata

Author(s): Watson DS, Brotherick I, Shenton BK, Wilson RG, Campbell FC

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 1999

Volume: 80

Issue: 7

Pages: 1062-1068

Print publication date: 07/05/1999

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.bjc.6690464

DOI: 10.1038/sj.bjc.6690464

PubMed id: 10362117

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