ABSTRACT
In a cancer cell, proliferation and apoptosis (collectively often referred to simply as 'growth') plus relationship to environ-
In simple terms, four key biologiG processes, ciS concep· Proliferation--cell cycle checkpoints tualized in Figure 3.2a,b and c, are critical to normal The cycle of cell replication consists of ·five phases, wl1ich
behavior of a cell:3 are critical to cancer development 1:FigU1·e 3.2c).4"The total
signal transduction growth factors
Disorders: failed deletion of mutated Glones
Proliferation
Growth lhom~1ostasis
Apoptosis
Control/ regulation: checkpoints in
cell cycle
Control/ regulation: norma I effector
mechanisms and triggering
epitl1el"lum
Initiated cells
Ben1gn neoplasia
Invasion
Malignant lesion (cancer)
1• 1 _./~~~Carcinogen . cau:>es genet1 ·~
·;<'"'?''"',- ... ,<i•~·.- ·1''"•'("u"" damage. '1 I. 1j \ \ I 1 ·.[ Apoptosis fails :.t~.IL _Lt:. __ ~.ILI to delete cell
. 1
Clonal expansion, with altered cell relationships developing
Malignan : conversion, with developed ability to invade, with or without altered proliferation and/ or apoptosis
0 j Tumor progression and generation of heterogeneity
duration varies from 12 to 48 hours, depending on conditions causing ct1anges in duration of G1 (the resting phase). In the colonic crypt, 10-20% of cells are capable of DNA synthesis and chromosomal duplication (the S phase), at any one time. They then move into G2 , which is the preparation for cell division, and then mitosis, or tt1e
(c) Mitotic checkpoint
Replication checkpoint
DNA damc1ge checkpoint
Figure 3.2 Main biological processes .inherent in control of cellular normality. (a) Conceptualization of growth control by regulated proliferation and apoptosis. (b) Conceptualization of morphologic progression through oncogenesis, inco~oorating altered cell relationships and invasion through basement membrane. Adapted from reference 3, with permission of publishers Lippmcott, Williams, and Wilkins. (c) Diagrammatic representation or the cell cvcle with Its phases and the key checkpoints that control genomic stability: M, mitosis, S, synthesis; G0 , terminal differentiation; G1 resting: G2 , preparation for mitOSIS.
