Two Functionally Distinct Classes of Growth Arrest States in Human Prokeratinocytes That Regulate Clonogenic Potential

Rapidly growing normal human neonatal prokeratinocytes (HPK) cultured in serum-free medium can be induced to undergo either reversible or irreversible growth arrest at distinct cell cycle states. Reversible G1 arrest was induced by culture of low-density cells in human lymphocyte conditioned medium, by culture in high-density stationary phase conditioned medium, and by culture in isoleucine-deficient medium. Irreversible arrest of HPK growth predominantly in G1 was induced by culture in growth factor-deficient medium. Irreversible arrest of HPK growth in G1 and G2 was also induced by culture in suspension in methylcellulose prepared in complete MCDB 153 medium or by culture in serum-containing medium. Finally, the drug razoxane was employed to induce irreversible arrest of HPK in G2. These data establish that there are 2 distinct classes of growth arrest states for HPK and suggest that each arrest mechanism may serve a unique role in the control of keratinocyte differentiation in normal cells. It is also possible that the development of selective defects in either of these processes could be of etiologic significance in certain epidermal disease states

A mutational hot spot in keratin 10 (KRT 10) in patients with epidermolytic hyperkeratosis

Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform erythroderma), is an autosomal dominant human skin disorder. Recently, we and others have described mutations in keratins 1 and 10 (K1 and K10) in patients with this disease. Structure-function models predict that these mutations would impair normal filament assembly and function. We have extended our earlier studies to include 8 more incidences of EHK. In half of these families, we were unable to locate a mutation within the rod domains of either K1 or K10. However, polymorphic restriction site and sequence analysis of the other families revealed a mutational hot spot within the 1A alpha-helical segment of K10. These involve Arginine to Histidine, Arginine to Cysteine and Arginine to Leucine substitutions at residue 10 of the rod domain. Interestingly, mutations in the corresponding Arginine residue in keratin K14 have been identified in patients with epidermolysis bullosa simplex. The large number of mutations found at this position in both keratins K10 and K14 suggests that other epithelia cell disorders will be discovered that are caused by the corresponding mutation in related type I keratin gene

Pediatric melanoma: Analysis of an international registry

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101810/1/cncr28289.pd

Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments

Regulation of Cellular Growth by 1,25-Dihydroxyvitamin D(3)-Mediated Growth Factor Expression

Although the primary function of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] is the regulation of calcium and phosphorus metabolism, it also regulates the growth and differentiation of several different cell types. Recent work suggests that 1,25(OH)(2)D(3) regulates cellular growth by altering the synthesis of growth factors and growth factor responses