Mulherkar Rita, Kirtane Bhakti M, Ramchandani Asha, Mansukhani Nirmala P, Kannan Sadhana, Naresh Kikkeri N
Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, India.
Oncogene. 2003 Apr 3;22(13):1936-44. doi: 10.1038/sj.onc.1206229.
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.
增强因子（EF）是一种生长因子调节剂，是人类分泌型II组磷脂酶A2的小鼠同源物。在表皮生长因子存在的情况下，EF在体外表现出促生长活性，还能使正常细胞发生表型转化。为了确定EF在体内的作用，使用人类角蛋白-14启动子异位驱动EF在鳞状上皮细胞中的表达。初代小鼠及其后代表现出异常的触须和鳞状、串珠状尾巴。在这些小鼠中，表皮的角化模式受到干扰，出现了角化不全和棘皮症。转基因小鼠TgK14-EF在尾巴表皮的基底层以上以及皮肤毛囊和皮脂腺的上皮细胞中表达EF。在其他鳞状上皮如颊黏膜、舌头和食道中也观察到EF的表达以及增生现象。转基因纯合的TgK14-EF小鼠虽然健康且可育，但毛发生长延迟且稀疏。半合子TgK14-EF小鼠对两阶段化学致癌作用敏感，在实验过程中比其正常同窝小鼠长出更多的乳头状瘤。转基因小鼠中乳头状瘤向癌的转化率高出两倍。
