Co-expression of p16<SUP>INK4A</SUP> and laminin 5 γ2 by microinvasive and superficial squamous cell carcinomas <i>in vivo</i> and by migrating wound and senescent keratinocytes in culture

作     者：Natarajan, E Saeb, M Crum, CP Woo, SB McKee, PH Rheinwald, JG 

作者机构：Harvard Univ Brigham & Womens Hosp Sch Med Dept Dermatol Boston MA 02115 USA Harvard Univ Brigham & Womens Hosp Sch Med Dept Pathol Boston MA 02115 USA Harvard Univ Sch Dent Med Dept Oral Med Infect & Immun Boston MA 02115 USA 

出 版 物：《AMERICAN JOURNAL OF PATHOLOGY》 (美国病理学杂志)

年 卷 期：2003年第163卷第2期

页      面：477-491页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NIAMS NIH HHS [P30-AR42689, P30 AR042689] Funding Source: Medline NIDCR NIH HHS [R01 DE013178, R01-DE13178] Funding Source: Medline 

主　　题：癌 鳞状细胞/代谢 癌 鳞状细胞/病理学 细胞黏附分子/代谢 细胞运动 细胞 培养的 周期素依赖激酶抑制剂p16/遗传学 周期素依赖激酶抑制剂p16/代谢 表皮/代谢 表皮/病理学 免疫组织化学 角蛋白细胞/细胞学 角蛋白细胞/代谢 口腔黏膜/细胞学 口腔黏膜/代谢 口腔黏膜/病理学 肿瘤侵润 蛋白质亚单位/代谢 皮肤肿瘤/代谢 皮肤肿瘤/病理学 伤口愈合 动物 人类 小鼠 

摘      要：The high frequency of mutation, deletion, and promoter silencing of the gene encoding p16(INK4A) (p16) in premalignant dysplasias and squamous cell carcinomas (SCC) of epidermis and oral epithelium classifies p16 as a tumor suppressor. However, the point during neoplastic progression at which this protein is expressed and presumably impedes formation of an SCC is unknown. induction of p16 has been found to be responsible for the senescence arrest of normal human keratinocytes in culture, suggesting the possibility that excessive or spatially abnormal cell growth in vivo triggers p16 expression. We examined 73 skin and oral mucosal biopsy specimens immunohistochemically to test this hypothesis. p16 was not detectable in benign hyperplastic lesions, but instead was expressed heterogeneously in some dysplastic and carcinoma in situ lesions and consistently at areas of microinvasion and at superficial margins of advanced SCCs. p16-positive cells in these regions coexpressed the gamma2 chain of laminin 5, identified previously as a marker of invasion in some carcinomas. Normal keratinocytes undergoing senescence arrest in culture proved to coordinately express p16 and gamma2 and this was frequently associated with increased directional motility. Keratinocytes at the edges of wounds made in confluent early passage cultures also coexpressed p16 and gamma2, accompanying migration to fill the wound. These results have identified the point during neoplastic progression in stratified squamous epithelial at which the tumor suppressor p16 is expressed and suggest that normal epithelia may use the same mechanism to generate non-dividing, motile cells for wound repair.