Proliferation markers

Abstract

Types of growth include embryonic, fetal, neonatal, juvenile and mature. Until full differentiation is achieved, cells grow through proliferation from progenitor cells. At maturity, the cellular genome is fixed with committed patterns of cell cycle duration and adaptation, ranging from static to renewing type 3. The static cell type cannot proliferate and adapts through hypertrophy. The renewing type continuously proliferates even without stimulus. In all cell types the processes of differentiation and proliferation are mutually exclusive. Cellular kinetics involve (a) the duration of the cell cycle, (b) the birth rate of cells, and (c) the growth rate fractions. The duration of the cell cycle is 2-4 days. All growth factors (GF) exert their influence during G1 phase. Release a GF by one cell type can influence the proliferation of another (= paracrine stimulation). At the end of G1 is the point of highest sensitivity to toxicity. Tumor suppressor genes act here through tyrosine phosphorylation. During S, the cell replicates its chromosomes. During G2 the immune surveillance and DNA damage repair mechanisms operate. Injured cells stay here longer enabling repair of their damaged DNA. Cell division involves both nuclear (mitosis) and cytoplasmic (cytokinesis) phases giving rise to 2 new cells. The cell cycle has 2 checkpoints. The first involves the G1-S transition and the second the G2-M transition. The types of cell cycle inhibition include (a) cycle- and phase-specific inhibition; (b) cycle-and nonphase-specific inhibition; (c) noncycle-and nonphase-specific inhibition, and finally (d) noncycle, nonphase-, and nonorgan-specific inhibition. Proliferation is a circadian process and it is stimulated by a variety of stimuli which include (1) interference with hormonal feedback pathways; (2) inhibition of the tissue trophic activity; (3) sustained presence of antigenic substances; (4) tissue ischemia; (5) changes of conditions luminally or on surfaces of tissues; (6) sustained cytotoxicity; (7) cell death; and (8) surgical resection. Proliferation can be arrested through senescence, apoptosis, injury or even during the development of immune cells. In the past, tissue/cell kinetics have been studied by tritiated thymidine histoautoradiography. Recently, monoclonal antibodies to proliferation-associated antigens, have been successfully employed. These antigens are cycle-associated proteins and include (1) PCNA; (2) p53; (3) Ki67; (4) AGNOR; (5) Statin; and (6) BrdU. Practical examples are given comparing PCNA and BrdU markers from 3 tissues, i.e. liver, glandular stomach, and uterus, across 2 or 3 strains of rats. Mean values of labeling indices are cited. Within the PCNA marker, 2 different clones are compared from the glandular stomach of SD rats of 2 different ages. Gender and across species comparisons are also made. All these comparisons denote that in every study where markers are used (a) there is a need for a concurrent study control group of the same age; (b) there is a need for in-house control data for this...

Neprilysin Null Mice Develop Exaggerated Pulmonary Vascular Remodeling in Response to Chronic Hypoxia

“…In vitro, we however have found that, when NEP is genetically eliminated, PA SMCs exhibit greater expression of select proliferation-associated biomarkers (PCNA, pERK, c-fos, and c-jun). 59,60 This suggests that NEP depletion promotes a proliferative milieu. In addition, it was found that PA SMCs from NEP Ϫ/Ϫ mice grow much faster than do PA SMCs from NEP ϩ/ϩ mice, which corroborates our observation of enhanced expression of proliferation-associated biomarkers in these cells.…”

Pulmonary Squamous Cyst Induced by Exposure to Indium Arsenide in Hamsters

“…For histological examination, sections were prepared as described in our previous study 4) . When localized hyperplastic lesions were obvious, the same sections were newly cut and proliferating activities measured with immunohistochemical staining of proliferating cell nuclear antigen (PCNA) 6) . The procedure was described in our previous report 5) .…”

Biomarkers for assessing reproductive development and health: Part 1--Pubertal development.

“…Some of those described to date include the presence of a parent compound or metabolite (Hecht 2002); proliferation and differentiation indices (Iatropoulos and Williams 1996); apoptotic end points (Samaha et al 1997); formation of DNA adducts or damage (Poirier and Weston 1996); chromosomal abnormalities (Lucas 1997); micronuclei formation (Schoket et al 1999); expression of specific genes (Riggins 2001); changes in gene expression profile (single or multiple genes) (Thomas et al 2001); and measurement of enzyme activity (Chen et al 1999), to name but a few. In some cases different biomarkers can be used to measure the same indicator.…”