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Review
. 2015 Jun;36 Suppl 1(Suppl 1):S38-60.
doi: 10.1093/carcin/bgv030.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling

Wilhelm Engström  1 , Philippa Darbre  2 , Staffan Eriksson  3 , Linda Gulliver  4 , Tove Hultman  5 , Michalis V Karamouzis  6 , James E Klaunig  7 , Rekha Mehta  8 , Kim Moorwood  9 , Thomas Sanderson  10 , Hideko Sone  11 , Pankaj Vadgama  12 , Gerard Wagemaker  13 , Andrew Ward  9 , Neetu Singh  14 , Fahd Al-Mulla  15 , Rabeah Al-Temaimi  15 , Amedeo Amedei  16 , Anna Maria Colacci  17 , Monica Vaccari  17 , Chiara Mondello  18 , A Ivana Scovassi  18 , Jayadev Raju  19 , Roslida A Hamid  20 , Lorenzo Memeo  21 , Stefano Forte  21 , Rabindra Roy  22 , Jordan Woodrick  22 , Hosni K Salem  23 , Elizabeth P Ryan  24 , Dustin G Brown  24 , William H Bisson  25
Affiliations
Review

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling

Wilhelm Engström et al. Carcinogenesis. 2015 Jun.

Abstract

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.

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Figures

Figure. 1.
Figure. 1.
Overview of the eukaryote cell cycle. For abbreviations and explanations, see text (12,13).
Figure. 2.
Figure. 2.
Exit from and re-entry into the cell cycle. This is according to a model based on cultured mouse 3T3 fibroblasts as described in detail elsewhere (15,16). For abbreviations and explanations, see text.
Figure. 3.
Figure. 3.
A simplified overview of key routes in intracellular signalling commencing with receptor activation of Ras (26–28).
Figure. 4.
Figure. 4.
The role of cyclins in the transition through various stages of the cell cycle. Cyclins associate with different cdks and their combined activities drive proliferating cells through checkpoints en route to mitosis in a concentration-dependent fashion. Each of the depicted cyclin–cdk complexes has antagonistic factors that will inhibit their action on cell cycle transit (reviewed in ref. 35).
Figure. 5.
Figure. 5.
The involvement of Myc in sustained cell proliferation.
Fig. 6.
Fig. 6.
The different human EGF receptors with respect to structure and function. For detailed explanation, see text (reviewed in ref. 52).
Fig. 7.
Fig. 7.
Topographical and functional distribution of disruptive chemicals. Numbers 1–9 correspond to headings in Table 1 and Supplementary Table 1. Redrawn from (1).
See this image and copyright information in PMC

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