Confirmation of the mapping of a 12‐<i>O</i>‐tetradecanoylphorbol‐13‐acetate promotion susceptibility locus, <i>Psl1</i>, to distal mouse chromosome 9

Angel, Joe M.; Caballero, Manuel; DiGiovanni, John

doi:10.1002/mc.10010

Cited by 11 publications

(18 citation statements)

References 44 publications

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“…Together, the data suggest that a gene(s) linked with the number of small colonies on chromosome 6, also influences the development of benign and malignant skin tumors. Finally, the Ksc1 locus on Chromosome 9 and two minor suggestive loci on chromosomes 7 and 6 are surprisingly close to loci found to be associated with skin tumor promotion (Angel et al, 1997(Angel et al, , 2001)/sensitivity/resistance to skin tumor development (Mock et al, 1998, Nagase et al, 1995. We hypothesize that the population of clonogenic keratinocytes able to produce small colonies represents a specific population of skin stem cells responsible for sensitivity or resistance to skin carcinogenesis.…”

Section: Discussionmentioning

confidence: 93%

Independent Inheritance of Genes Regulating Two Subpopulations of Mouse Clonogenic Keratinocyte Stem Cells

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Suleimanian

Stepanova

et al. 2004

Journal of Investigative Dermatology Symposium Proceedings

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Mouse keratinocyte stem cells originate from the bulge of hair follicle, and, according to definition, possess a clonogenic activity in vitro. We have investigated seven inbred (C57BL/6, C3H, DBA/2, BALB/c, FVB) and outbred (SENCAR, CD-1) mouse strains and found that three genetically distinct subsets of mouse strains differ significantly in the frequency of clonogenic activity in vitro. The analysis of keratinocyte colonies in two reciprocal backcross [C57BL/6 x (BALB/c x C57BL/6); BALB/c x (BALB/c x C57BL/6)] and intercross [(BALB/c x C57BL/ 6)F2] of BALB/c and C57BL/6 mice allowed us to identify two subpopulations of clonogenic keratinocytes able to produce small (less than 2 mm2) and large (more than 2 mm2) colonies. We conducted linkage analysis and found that small colonies associated with mouse chromosomes 1, 6, 7, 8, and 9; but large colonies--with the chromosome 4. We defined locus on the chromosome 9 that associated with small colonies as keratinocyte stem cell locus 1 (Ksc1), and locus on the mouse chromosome 4 associated with large colonies-keratinocyte stem cell locus 2 (Ksc2). Ksc1 and loci on chromosomes 6 and 7 are close if not equal to loci associated with sensitivity to skin carcinogenesis. We conclude that two subpopulations of stem cells able to produce small and large colonies regulated by different genes and genes regulating small colonies might be responsible for sensitivity to skin carcinogenesis.

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Section: Discussionmentioning

confidence: 93%

Independent Inheritance of Genes Regulating Two Subpopulations of Mouse Clonogenic Keratinocyte Stem Cells

Попова

Suleimanian

Stepanova

et al. 2004

Journal of Investigative Dermatology Symposium Proceedings

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“…These genetically controlled signaling pathways are becoming more clear, but much remains to be learned about this intricate system and how it is modulated during carcinogenesis and tumor promotion in skin [reviewed in [13]]. Our previous studies demonstrated that genetic control of susceptibility to skin tumor promotion by TPA in crosses between susceptible DBA/2J and resistant C57BL/6J mice is a multigenic trait [16–20]. We have mapped promotion susceptibility loci to mouse chromosomes (chr) 1 ( Psl3 ), 2 ( Psl2 ), 9 ( Psl1 ), and 19 ( Psl4 ) [17–20].…”

Section: Introductionmentioning

confidence: 99%

Differential gene expression in epidermis of mice sensitive and resistant to phorbol ester skin tumor promotion

Riggs

Angel

Abel

et al. 2005

Molecular Carcinogenesis

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Previous data from two-stage carcinogenesis studies in mouse skin demonstrated that genetic control of susceptibility to skin tumor promotion by the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), in crosses between susceptible DBA/2J and resistant C57BL/6J mice is a multigenic trait. Utilizing a cDNA microarray approach, we compared global gene expression profiles in the epidermis of these two mouse strains treated with TPA or vehicle (acetone). Gene expression in the epidermis was analyzed after the treatment to identify global effects of TPA, as well as potential candidate genes that modify susceptibility to skin tumor promotion. DBA/2J and C57BL/6J mice were treated topically four times with 3.4 nmol TPA or acetone over a 2-wk period, and RNA was extracted from epidermis 6 h after the final treatment. Labeled cDNA generated from each group was hybridized to commercial cDNA microarrays (Agilent) containing more than 8000 targets. More than 450 genes were significantly influenced, directly or indirectly, by TPA treatment in the epidermis of either strain. Notably, 44 genes exhibited differential expression between the tumor promotion sensitive and resistant mouse strains. Several genes that were differentially expressed in DBA/2J versus C57BL/6J epidermis after TPA treatment were located in chromosomal regions linked to TPA promotion susceptibility. Three genes, Gsta4, Nmes1 (MGC58382), and Serpinb2, located within promotion susceptibility loci Psl1 (chr 9), Psl2 (chr 2), and Psl3 (chr 1), respectively, were identified in this analysis as potential candidates for modifiers of susceptibility to skin tumor promotion by TPA.

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“…As noted in the Introduction , the skin tumor promotion susceptibility locus, Psl1 , maps to the distal half of chr 9 (Angel et al 1997, 2001, 2010; Angel and Digiovanni 1999; Abel et al 2010). We recently reported that when initiated with 2.5 μmol of N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG) and promoted twice weekly with 13.6 nmol of TPA for 36 weeks, the congenic mouse strain, C57BL/6.Psl1A dba , which inherited a 59.1-Mb region of chr 9 (distal to D9Mit316 ) from DBA/2 (Figure 1), was significantly more sensitive to skin tumor promotion than C57BL/6 controls (Abel et al 2010).…”

Section: Resultsmentioning

confidence: 97%

“…The skin tumor promotion susceptibility locus, Psl1 , was previously mapped to a 59.1-Mb region of mouse chr 9 (Angel et al 1997, 2001, 2010; Angel and Digiovanni 1999) and the glutathione S-transferase gene, Gsta4 , was shown to underlie at least some of the effect of this locus on skin tumor promotion susceptibility in mice (Abel et al 2010). In addition, GSTA4 has been shown to be a modifier of susceptibility to nonmelanoma skin cancer in humans (Abel et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Our laboratory, as well as others, has identified genetic loci that modify susceptibility to skin tumor promotion by 12- O -tetradecanoylphorbol-13-acetate (TPA), showing that susceptibility to skin tumor promotion is a multigenic trait (Nagase et al 1995; Angel et al 1997; Mock et al 1998; Angel and Digiovanni 1999; Nagase et al 1999; Angel et al 2001; Peissel et al 2001; Angel et al 2003; Fujiwara et al 2007). We previously mapped TPA promotion susceptibility loci to chromosomes (chr) 1 ( Psl3 ), 2 ( Psl2 ), 9 ( Psl1 ), and 19 ( Psl4 ) in genetic crosses of C57BL/6 with DBA/2 mice (Angel et al 1997; Angel and Digiovanni 1999; Angel et al 2001, 2003) and recently reported that Psl1 consists of at least two subloci, Psl1.1 and Psl1.2 (Abel et al 2010). From these earlier studies, glutathione S-transferase alpha 4 ( Gsta4 ) was identified as a skin tumor promotion susceptibility gene that maps within the Psl1.2 locus (Abel et al 2010).…”

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confidence: 96%

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Fine Mapping Reveals That Promotion Susceptibility Locus 1 (Psl1) Is a Compound Locus With Multiple Genes That Modify Susceptibility to Skin Tumor Development

Angel

Abel

Riggs

et al. 2014

G3 Genes|Genomes|Genetics

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Although it is well known that the majority of human cancers occur as the result of exposure to environmental carcinogens, it is clear that not all individuals exposed to a specific environmental carcinogen have the same risk of developing cancer. Considerable evidence indicates that common allelic variants of low-penetrance, tumor susceptibility genes are responsible for this interindividual variation in risk. We previously reported a skin tumor promotion susceptibility locus, Psl1, which maps to the distal portion of chromosome 9, that modified skin tumor promotion susceptibility in the mouse. Furthermore, Psl1 was shown to consist of at least two subloci (i.e., Psl1.1 and Psl1.2) and that glutathione S-transferase alpha 4 (Gsta4), which maps to Psl1.2, is a skin tumor promotion susceptibility gene. Finally, variants of human GSTA4 were found to be associated with risk of nonmelanoma skin cancer. In the current study, a combination of nested and contiguous C57BL/6 congenic mouse strains, each inheriting a different portion of the Psl1 locus from DBA/2, were tested for susceptibility to skin tumor promotion with 12-O-tetradecanoylphorbol-13-acetate. These analyses indicate that Psl1 is a compound locus with at least six genes, including Gsta4, that modify skin tumor promotion susceptibility. More than 550 protein-coding genes map within the Psl1 locus. Fine mapping of the Psl1 locus, along with two-strain haplotype analysis, gene expression analysis, and the identification of genes with amino acid variants, has produced a list of fewer than 25 candidate skin tumor promotion susceptibility genes.

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Confirmation of the mapping of a 12‐O‐tetradecanoylphorbol‐13‐acetate promotion susceptibility locus, Psl1, to distal mouse chromosome 9

Cited by 11 publications

References 44 publications

Independent Inheritance of Genes Regulating Two Subpopulations of Mouse Clonogenic Keratinocyte Stem Cells

Independent Inheritance of Genes Regulating Two Subpopulations of Mouse Clonogenic Keratinocyte Stem Cells

Differential gene expression in epidermis of mice sensitive and resistant to phorbol ester skin tumor promotion

Fine Mapping Reveals That Promotion Susceptibility Locus 1 (Psl1) Is a Compound Locus With Multiple Genes That Modify Susceptibility to Skin Tumor Development

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