Increased apoptosis accompanies neoplastic development in the human colorectum

Frank A Sinicrope, Gardiner Roddey, Timothy J. McDonnell, Yu Shen, Karen R. Cleary, L. Clifton Stephens

Research output: Contribution to journalArticle

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Abstract

A disturbance in the balance between cell proliferation and cell loss, or apoptosis, may underlie neoplastic development. Therefore, we determined spontaneous apoptotic and proliferative rates in normal, hyperplastic, adenomatous, and malignant colorectal epithelia. In paired sections, DNA strand breaks were detected using the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, and apoptotic cells were also identified in H and E-stained slides by morphological criteria. Cell proliferation, bcl-2, and p53 expression were analyzed using specific monoclonal antibodies. In normal mucosa, luminal epithelial cells demonstrated higher rates of apoptosis compared to cells in the proliferative zone. Neoplastic transformation was associated with a significant increase in rates of apoptosis and proliferation. However, apoptosis, but not proliferation, decreased at the adenoma-to-carcinoma transition coincident with expression of mutant p53. In carcinomas, both mutant p53 and bcl-2 protein levels were associated with attenuated apoptotic rates. In conclusion, apoptosis is an important regulator of growth in normal and neoplastic colorectal epithelia. Increased apoptosis and proliferation accompany neoplastic transformation, suggesting that an alteration in apoptotic rates is an important event in colorectal carcinogenesis. Furthermore, the imbalance in these processes found in carcinomas may facilitate tumor growth and progression.

Original languageEnglish (US)
Pages (from-to)1999-2006
Number of pages8
JournalClinical Cancer Research
Volume2
Issue number12
StatePublished - Dec 1996

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Human Development
Apoptosis
Carcinoma
Epithelium
Cell Proliferation
DNA Breaks
DNA Nucleotidylexotransferase
Growth
Adenoma
Carcinogenesis
Mucous Membrane
Epithelial Cells
Monoclonal Antibodies
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sinicrope, F. A., Roddey, G., McDonnell, T. J., Shen, Y., Cleary, K. R., & Stephens, L. C. (1996). Increased apoptosis accompanies neoplastic development in the human colorectum. Clinical Cancer Research, 2(12), 1999-2006.

Increased apoptosis accompanies neoplastic development in the human colorectum. / Sinicrope, Frank A; Roddey, Gardiner; McDonnell, Timothy J.; Shen, Yu; Cleary, Karen R.; Stephens, L. Clifton.

In: Clinical Cancer Research, Vol. 2, No. 12, 12.1996, p. 1999-2006.

Research output: Contribution to journalArticle

Sinicrope, FA, Roddey, G, McDonnell, TJ, Shen, Y, Cleary, KR & Stephens, LC 1996, 'Increased apoptosis accompanies neoplastic development in the human colorectum', Clinical Cancer Research, vol. 2, no. 12, pp. 1999-2006.
Sinicrope FA, Roddey G, McDonnell TJ, Shen Y, Cleary KR, Stephens LC. Increased apoptosis accompanies neoplastic development in the human colorectum. Clinical Cancer Research. 1996 Dec;2(12):1999-2006.
Sinicrope, Frank A ; Roddey, Gardiner ; McDonnell, Timothy J. ; Shen, Yu ; Cleary, Karen R. ; Stephens, L. Clifton. / Increased apoptosis accompanies neoplastic development in the human colorectum. In: Clinical Cancer Research. 1996 ; Vol. 2, No. 12. pp. 1999-2006.
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