Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice.

Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice. Research Abstract Details 

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Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice. Abstract Text:

Robert W Engelman,Rosalind J Jackson,Domenico Coppola,Walker Wharton,Alan B Cantor,W Jack Pledger,

p21(Cip1/WAF1) localizes to the nucleus in response to gamma-irradiation induced DNA damage and mediates a G(1) checkpoint arrest. Although gamma-irradiated p21(+/-) mice develop a broad spectrum of tumors, gamma-irradiated p21(-/-) mice develop significantly more metastatic cancers. To evaluate the expression of p21 in tissues prone or resistant to tumorigenesis as a function of gamma-irradiation, and to determine whether phenotypic loss of p21 heterozygosity occurs during tumor progression in p21(+/-) mice, tissues and tumors from gamma-irradiated mice were evaluated immunohistochemically. The percentage of tumors in p21(+/-) mice that were nuclear p21-positive declined with progression to metastasis (p<0.0001). Benign tumors were more often p21-positive and comprised of larger subsets of nuclear p21-positive cells than were malignant tumors of the same histopathological type, while metastatic cancers were nuclear p21-negative (p=0.0003). Even when a primary cancer was comprised of a subset of nuclear p21-positive cells, the metastatic foci of that same cancer were nuclear p21-negative. Mesenchymal tumors, though rare, were more likely metastatic than were epithelial tumors (p=0.0004), and these were invariably nuclear p21-negative. Prepubescent epithelial tissues from which most tumors later originated in mice with reduced p21 gene dosage (i.e., harderian gland, ovary, small intestine, and lung) were p21 expressive within 4 h of gamma-irradiation (p=0.0625), so that p21/Ki67 ratios increased post-gamma-irradiation (p=0.03). In contrast, p21 did not localize to nuclei of cortical thymocytes, a tissue where tumorigenesis was not augmented by reduced p21 gene dosage. Cellular subclones of malignant tumors, especially those of mesenchymal cell origin, which lack nuclear p21 may more readily acquire the genetic alterations of the metastatic phenotype.

Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice. Publishing Authors By Initials

RW Engelman,RJ Jackson,D Coppola,W Wharton,AB Cantor,WJ Pledger,

For similar neoplasms: neoplasms, radiation-induced research abstracts see: neoplasms: neoplasms, radiation-induced research

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Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental and molecular pathology

VOLUME: 82

Page Numbers: 234-44

Journal Abbreviation: Exp. Mol. Pathol.

ISSN: 0014-4800

DAY: 4

MONTH: 01

YEAR: 2007

Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice. Information

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LANGUAGE: eng

NlmUniqueID: 370711

Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice. Keywords Mesh Terms:

KEYWORDS: Neoplasms, Radiation-Induced

MESH TERMS: pathology

Chemical & Substance for Abstract: Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice. Information

Substance Name: Ki-67 Antigen

Registry Number: 0

Grant and Affiliation Information for Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice.

AFFILIATION: Department of Pathology and Cell Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. engelman@moffitt.usf.edu

Country: United States

AGENCY: United States NCI

GRANT: CA78038

ACRONYM: CA

MEDLINETA: Exp Mol Pathol

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