MUC1 regulates cyclin D1 gene expression through p120 catenin and ß-catenin.

MUC1 interacts with ß-catenin and p120 catenin to modulate WNT signaling. We investigated the effect of overexpressing MUC1 on the regulation of cyclin D1, a downstream target for the WNT/ß-catenin signaling pathway, in two human pancreatic cancer cell lines, Panc-1 and S2-013. We observed a significant enhancement in the activation of cyclin D1 promoter-reporter activity in poorly differentiated Panc1.MUC1F cells that overexpress recombinant MUC1 relative to Panc-1.NEO cells, which express very low levels of endogenous MUC1. In stark contrast, cyclin D1 promoter activity was not affected in moderately differentiated S2-013.MUC1F cells that overexpressed recombinant MUC1 relative to S2-013.NEO cells that expressed low levels of endogenous MUC1. The S2-013 cell line was recently shown to be deficient in p120 catenin. MUC1 is known to interact with P120 catenin. We show here that re-expression of different isoforms of p120 catenin restored cyclin D1 promoter activity. Further, MUC1 affected subcellular localization of p120 catenin in association with one of the main effectors of P120 catenin, the transcriptional repressor Kaiso, supporting the hypothesis that p120 catenin relieved transcriptional repression by Kaiso. Thus, full activation of cyclin D1 promoter activity requires ß-catenin activation of TCF-lef and stabilization of specific p120 catenin isoforms to relieve the repression of KAISO. Our data show MUC1 enhances the activities of both ß-catenin and p120 catenin.

Brief report: A case of autism with interstitial deletion of chromosome 13.

A case of an 18-year-old male who meets the DSM-IV criteria for autistic disorder and borderline intelligence is described. Cytogenetic evaluation revealed a karyotype of 46, XY, del(13)(q14q22). The relevance of this case to the etiology of autism is discussed.

Child psychiatry practice patterns in Ontario.

OBJECTIVES: To examine the demographics, training, distribution, venues of practice, remuneration patterns, and professional affiliations of child psychiatrists in Ontario. METHOD: In July 1997, questionnaires were sent to 229 Ontario psychiatrists. A second mailing was sent to nonresponders in the fall of 1997. The overall response rate was 66.8%. RESULTS: Compared with other research regarding the ratio of child psychiatrists to children with mental health problems, Ontario fares relatively well (1:6148). Generally, Ontario child psychiatrists report having received formalized training in the speciality. Child psychiatrists are disproportionately concentrated in Toronto and in midsize cities with medical schools compared with rural regions. Out-reach services to smaller communities are provided by 30% of child psychiatrists, but it is not clear whether the services are sufficient and equitably available. Approximately 50% of current psychiatrists will be aged 65 years or older in 15 years, and it is unclear whether sufficient numbers will replace them. The profession appears to be reaching an equitable gender representation. Most child psychiatrists belong to the professional organizations that support the profession; however, they are least likely to belong to the Ontario Psychiatric Association (OPA). CONCLUSIONS: An optimal ratio of child psychiatrists per population served still needs to be determined, with special consideration given to the needs of rural communities. The small ratio of child psychiatrists to the population of children with mental health needs highlights the importance of collaborating with other medical and mental health professionals. Recruiting and retaining child psychiatrists will need to be monitored. Child psychiatrists in Ontario need a unified voice to address these issues.

Teaching child and adolescent psychiatry to family medicine trainees: a pilot experience.

OBJECTIVE: To develop learning objectives for teaching child psychiatry to family medicine trainees and to evaluate the best method of teaching these objectives. METHOD: For this descriptive study, knowledge, attitude, and skill objectives were presented to trainees at the start of a 6-month rotation, and an evaluation mechanism was developed based on the learning objectives. The method of instruction in each of the training locations was described independently by the child psychiatry consultant and attending family physician. The trainees' evaluations were presented according to training locations. RESULTS: Family medicine trainees perceived the teaching-consultation method, with live interviews, to be the most helpful and the didactic lecture format to be least helpful. CONCLUSION: The importance of teaching family medicine residents to recognize mental health problems in children and adolescents, preferably by using live interviews, and the implications for postresidency practice are emphasized.