PAX8 promotes tumor cell growth by transcriptionally regulating E2F1 and stabilizing RB protein.

The retinoblastoma protein (RB)-E2F1 pathway has a central role in regulating the cell cycle. Several PAX proteins (tissue-specific developmental regulators), including PAX8, interact with the RB protein, and thus regulate the cell cycle directly or indirectly. Here, we report that PAX8 expression is frequent in renal cell carcinoma, bladder, ovarian and thyroid cancer cell lines, and that silencing of PAX8 in cancer cell lines leads to a striking reduction in the expression of E2F1 and its target genes, as well as a proteasome-dependent destabilization of RB protein, with the RB1 mRNA level remaining unaffected. Cancer cells expressing PAX8 undergo a G(1)/S arrest and eventually senesce following PAX8 silencing. We demonstrate that PAX8 transcriptionally regulates the E2F1 promoter directly, and E2F1 transcription is enhanced after RB depletion. RB is recruited to the PAX8-binding site, and is involved in PAX8-mediated E2F1 transcription in cancer cells. Therefore, our results suggest that, in cancer, frequent and persistent expression of PAX8 is required for cell growth control through transcriptional activation of E2F1 expression and upregulation of the RB-E2F1 pathway.

Oral health of individuals aged 3-80 years in Jönköping, Sweden in 1973 and 1983. I. A review of findings on dental care habits and knowledge of oral health.

The aim of the present study was to present data from dental care habits and knowledge of oral health in two cross-sectional studies carried out in 1973 and 1983. A random sample of approximately 1000 individuals evenly distributed in the age groups 3, 5, 10, 15, 20, 30, 40, 50, 60 and 70 years was studied for each of these two years. In the 1983-year examination 80 individuals 80 years of age were also included. All subjects were inhabitants of the community of Jönköping, Sweden. A questionnaire about dental care habits and knowledge was used in combination with a clinical and radiographical examination. The participants answered 23-101 questions. The same questions were raised in 1973 and 1983. For most age groups more then 80 per cent visited a dentist yearly in 1983. This yearly attendance was higher than that for 1973. In the 20-year-old group 14 per cent of the individuals received dental care in the PDS in 1973 compared to 63 per cent in 1983. The main reason to visit a dentist in 1973 was by the patient's own initiative while in 1983 the appointments were based on the dentist's initiative. The number of subjects that felt discomfort in connection with a visit to the dentist had decreased between 1973 and 1983. Knowledge about the etiology of caries had increased between 1973 and 1983 was not the case for gingivitis and periodontitis. An increase had occurred in toothbrushing frequency and the use of toothpicks and disclosing tablets but this between 1973 and 1983. In 1983, 98 to 93 per cent of the subjects in the age groups 10-30 years had been exposed to topical fluorides. The corresponding figure for 30-year-olds in 1973 was 1 per cent. It is obvious that during the period 1973 to 1983 there has been an increase in dental attendance, knowledge of dental diseases, oral health and the use of preventive measures.

Oral health of individuals aged 3-80 years in Jönköping, Sweden, in 1973 and 1983. II. A review of clinical and radiographic findings.

The aim of this study was to present data from clinical and radiographic examinations on oral health in two cross-sectional studies carried out in 1973 and 1983. A random sample of approximately 1000 individuals, evenly distributed in the age groups 3, 5, 10, 15, 20, 30, 40, 50, 60 and 70 years was studied for each of these two years. In the 1983-year examination 80 individuals, 80 years of age, were also included. All subjects were inhabitants of the community of Jönköping, Sweden. The clinical and radiographic examination assessed edentulousness, removable dentures, number of teeth, caries, restorations and overhangs, gingival and periodontal status, oral hygiene and calculus, endodontic treatment and periapical status. A reduction in number of edentulous individuals by 25% was recorded between the two examinations. This was matched by an increase in the mean number of teeth, mainly of molars. The largest difference in mean number of teeth between the 1973 and 1983 examinations was found for the 70-year-olds. These were 8.5 and 11.8 teeth respectively. The younger age groups showed an increase in the proportion of individuals free from caries and restorations. In 1973 the caries-free proportions were 35% for 3-year-olds and 9% for 5-year-olds. In 1983 these values had improved to 70% and 29% respectively. Corresponding to this trend the number of decayed tooth surfaces was lower in 1983. Fewer filled tooth surfaces were present 1983 compared with 1973 for the age groups 10, 15, 20 and 30 years but higher for the age groups 5, 50 and 60 years and unchanged for the remaining groups. For the younger age groups the overall reduction in DFS was about 50% but this increased to 90% for buccal and lingual surfaces. Both secondary caries and overhanging restorations had decreased in the 1983 group for all ages. At least 75-86% of restorations were without overhangs in 1983 compared to 47-65% in 1973. Gingival health had improved over the 10-year period. Sites with plaque and calculus and gingival units exhibiting gingivitis had all decreased in frequency by 1983. Buccal surfaces showed the greatest improvement. The frequency of individuals with one or more periodontal pockets (greater than or equal to 4 mm) increased with age but was of the same distribution in 1983 as in 1973.(ABSTRACT TRUNCATED AT 400 WORDS)