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A Model for UV-Induction of Skin Cancer.

Ouhtit A, Ananthaswamy HN - J. Biomed. Biotechnol. (2001)

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The cellular and molecular events that contribute to thedevelopment of UV-induced skin cancer is a complex processinvolving at least two distinct pathways that interact or convergeto cause skin cancer (Figure 1)... One pathway involves the action of UV on target cells (keratinocytes) for neoplastic transformation, and the otherinvolves the effects of UV on the host's immune system .There is evidence to indicate that UV-induced DNA damage plays animportant role in both pathways... Some of the molecular events that occur in cellsfollowing UV exposure are DNA damage, induction of p53 andp53-regulated proteins, cell cycle arrest, DNA repair, andapoptosis... Interestingly, we haverecently demonstrated that p53 may up-regulate bax anddown-regulate Bcl-2 protein resulting in apoptosis andthat Fas/Fas-ligand pathway is essential for UV-inducedapoptosis... Following chronic UV exposure, errors associated with DNA repairand/or replication can result into mutations in the p53gene, especially C → T or CC → TT transitions,considered as UV-molecular signature... Because cells containing p53mutations are relatively more resistant to UV-induced apoptosis,they can acquire a growth advantage... It is likely that themutated cells expand preferentially in a clonal fashion at theexpense of the normal surrounding keratinocytes, that commitmassive suicide by apoptosis, leading to the appearance of p53mutated clones in the epidermis... Thus, another tumor suppressor geneknown as patched (ptc) has been implicated inthe development of basal cell carcinoma (BCC)... The human ptc gene was found to colocalize with the maplocation of nevoid basal cell carcinoma syndrome (NBCCS) onchromosome 9 at 9q22.3... Studies of NBCCS patients haveshown that they have both genomic and sporadic mutations in theptc gene, suggesting that these mutations are theultimate cause of this disease... Sporadic ptc mutationshave been found in BCC from otherwise normal individuals, some ofwhich are UV-signature, either C → T orCC → TT changes... However, ptc mutations havenot been reported in SCC... Nonetheless, these results suggest thatgenetic alterations in the ptc gene may also play a rolein the development of BCC.

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Pathways involved in skin cancer development.
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Figure 1: Pathways involved in skin cancer development.

Mentions: The cellular and molecular events that contribute to thedevelopment of UV-induced skin cancer is a complex processinvolving at least two distinct pathways that interact or convergeto cause skin cancer (Figure 1). One pathway involves the action of UV on target cells (keratinocytes) for neoplastic transformation, and the otherinvolves the effects of UV on the host's immune system [1].There is evidence to indicate that UV-induced DNA damage plays animportant role in both pathways.


A Model for UV-Induction of Skin Cancer.

Ouhtit A, Ananthaswamy HN - J. Biomed. Biotechnol. (2001)

Pathways involved in skin cancer development.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC79671&req=5

Figure 1: Pathways involved in skin cancer development.
Mentions: The cellular and molecular events that contribute to thedevelopment of UV-induced skin cancer is a complex processinvolving at least two distinct pathways that interact or convergeto cause skin cancer (Figure 1). One pathway involves the action of UV on target cells (keratinocytes) for neoplastic transformation, and the otherinvolves the effects of UV on the host's immune system [1].There is evidence to indicate that UV-induced DNA damage plays animportant role in both pathways.

View Article: PubMed Central - HTML - PubMed

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The cellular and molecular events that contribute to thedevelopment of UV-induced skin cancer is a complex processinvolving at least two distinct pathways that interact or convergeto cause skin cancer (Figure 1)... One pathway involves the action of UV on target cells (keratinocytes) for neoplastic transformation, and the otherinvolves the effects of UV on the host's immune system .There is evidence to indicate that UV-induced DNA damage plays animportant role in both pathways... Some of the molecular events that occur in cellsfollowing UV exposure are DNA damage, induction of p53 andp53-regulated proteins, cell cycle arrest, DNA repair, andapoptosis... Interestingly, we haverecently demonstrated that p53 may up-regulate bax anddown-regulate Bcl-2 protein resulting in apoptosis andthat Fas/Fas-ligand pathway is essential for UV-inducedapoptosis... Following chronic UV exposure, errors associated with DNA repairand/or replication can result into mutations in the p53gene, especially C → T or CC → TT transitions,considered as UV-molecular signature... Because cells containing p53mutations are relatively more resistant to UV-induced apoptosis,they can acquire a growth advantage... It is likely that themutated cells expand preferentially in a clonal fashion at theexpense of the normal surrounding keratinocytes, that commitmassive suicide by apoptosis, leading to the appearance of p53mutated clones in the epidermis... Thus, another tumor suppressor geneknown as patched (ptc) has been implicated inthe development of basal cell carcinoma (BCC)... The human ptc gene was found to colocalize with the maplocation of nevoid basal cell carcinoma syndrome (NBCCS) onchromosome 9 at 9q22.3... Studies of NBCCS patients haveshown that they have both genomic and sporadic mutations in theptc gene, suggesting that these mutations are theultimate cause of this disease... Sporadic ptc mutationshave been found in BCC from otherwise normal individuals, some ofwhich are UV-signature, either C → T orCC → TT changes... However, ptc mutations havenot been reported in SCC... Nonetheless, these results suggest thatgenetic alterations in the ptc gene may also play a rolein the development of BCC.

No MeSH data available.


Related in: MedlinePlus