Helander S D, Peters M S, Pittelkow M R
Department of Dermatology, Mayo Clinic, Rochester, MN 55905.
J Am Acad Dermatol. 1993 Nov;29(5 Pt 1):741-8. doi: 10.1016/0190-9622(93)70240-t.
p53 is an oncogene and a tumor-suppressor gene whose gene product regulates the cell growth cycle. Mutations in p53 are the most common genetic alterations in human cancer.
Our purpose was to define p53 expression and subcellular localization in normal and pathologic epidermis.
We examined sections of normal skin, psoriasis, squamous cell carcinoma (SCC), basal cell carcinoma (BCC), keratoacanthoma, and cultured epithelial cell lines with five antibodies to p53.
Monoclonal antibody MAb421 and MAb1801 stained the cytoplasm of normal basal keratinocytes, suggesting that subcellular localization or sequestration of wild-type p53 regulates its activity. Polyclonal antibody reacted throughout normal epidermis, suggesting heterogeneity of species or conformational forms of p53 protein. Cytoplasmic reactivity to MAb421 was similar in normal epidermis, psoriasis, and cultured keratinocytes but was, diminished in SCC, BCC, and keratoacanthoma. CM-1 reactivity persisted in these tumors. Putative p53 mutations detected by MAb240 reactivity were present in 44% of SCC specimens.
Epidermis expresses p53 and the gene may regulate epidermal keratinocyte growth and carcinogenesis.
p53是一种癌基因和肿瘤抑制基因,其基因产物调节细胞生长周期。p53突变是人类癌症中最常见的基因改变。
我们的目的是确定正常和病理表皮中p53的表达及亚细胞定位。
我们用五种针对p53的抗体检查了正常皮肤、银屑病、鳞状细胞癌(SCC)、基底细胞癌(BCC)、角化棘皮瘤的切片以及培养的上皮细胞系。
单克隆抗体MAb421和MAb1801对正常基底角质形成细胞的细胞质染色,提示野生型p53的亚细胞定位或隔离调节其活性。多克隆抗体在整个正常表皮中均有反应,提示p53蛋白的物种或构象形式存在异质性。在正常表皮、银屑病和培养的角质形成细胞中,对MAb421的细胞质反应相似,但在SCC、BCC和角化棘皮瘤中减弱。CM-1反应在这些肿瘤中持续存在。通过MAb240反应检测到的假定p53突变存在于44%的SCC标本中。
表皮表达p53,该基因可能调节表皮角质形成细胞的生长和致癌作用。