Expression of enhancing factor/phospholipase A2 in skin results in abnormal epidermis and increased sensitivity to chemical carcinogenesis.
Enhancing factor (EF), a growth factor modulator, is the mouse homologue of human secretory group II phospholipase A(2). EF exhibits growth-promoting activity in vitro, in the presence of epidermal growth factor, and also brings about phenotypic transformation of normal cells. In order to ascertain the role of EF in vivo, a human keratin-14 promoter was used to drive the expression of EF ectopically to squamous epithelial cells. The founder mouse and its progeny showed abnormal whiskers and a scaly, beaded tail. In these mice, keratinization pattern of the epidermis was disturbed and parakeratosis and acanthosis were noted. The transgenic mice, TgK14-EF, expressed EF in the suprabasal layers of tail epidermis as well as in the epithelial cells of hair follicle and sebaceous glands of skin. Expression of EF along with hyperplasia was also observed in other squamous epithelia such as buccal mucosa, tongue and oesophagus. TgK14-EF mice homozygous for the transgene showed delayed and scanty hair growth although the mice were healthy and fertile. The hemizygous TgK14-EF mice were sensitive to a two-stage chemical carcinogenesis and developed a higher number of papillomas than their normal littermates over the course of the experiment. The conversion rate of papilloma to carcinoma was two fold higher in the transgenic mice.
Mulherkar
Rita
R
Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, India. cri3@soochak.ncst.ernet.in
Kirtane
Bhakti M
BM
Ramchandani
Asha
A
Mansukhani
Nirmala P
NP
Kannan
Sadhana
S
Naresh
Kikkeri N
KN
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000235:genetics; D004817:Epidermis / Q000002:abnormalities*; D005354:Fibrosarcoma / Q000139:chemically induced / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054501:Group II Phospholipases A2; D006801:Humans; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018295:Neoplasms, Basal Cell / Q000139:chemically induced / Q000235:genetics; D010212:Papilloma / Q000139:chemically induced* / Q000235:genetics; D010641:Phenotype; D010741:Phospholipases A / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012867:Skin / Q000201:enzymology*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics; D013623:Tail / Q000002:abnormalities / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D019076:Transgenes; D014738:Vibrissae / Q000002:abnormalities
D002273:Carcinogens; D011993:Recombinant Fusion Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C516288:Pla2g2a protein, mouse; D013755:Tetradecanoylphorbol Acetate