ABSTRACT
Overexpression of focal adhesion kinase (FAK) has been well correlated with tumor development and/or the maintenance of tumor phenotype. In addition, inappropriate activation of the extracellular regulated kinase (ERK) signaling pathway is common to many human cancers. In the present study, we investigated the interplay between FAK and ERK in androgen-independent prostate cancer cells (PC3 and DU145 cells). We observed that suppression of FAK expression using small interfering RNA-mediated knockdown decreased the clonogenic activity, whereas overexpression of FAK increased it. We also observed that detachment of PC3 and DU145 cells from their substrate induced tyrosine phosphorylation of FAK. ERK knockdown diminished FAK protein levels and tyrosine phosphorylation of FAK as well as FAK promoter-reporter activity. We also tested the effect of MEK inhibitors and small interfering RNA-mediated knockdown of ERK1 and/or ERK2 on cell proliferation, invasiveness, and growth in soft agar of PC3 and DU145 cells. Inhibition of ERK signaling grossly impaired clonogenicity as well as invasion through Matrigel. However, inhibition of ERK signaling resulted in only a modest inhibition of 3H-thymidine incorporation and no effect on overall viability of the cells or increased sensitivity to anoikis. Taken together, these data show, for the first time, a requirement for FAK in aggressive phenotype of prostate cancer cells; reveal interdependence of FAK and ERK1/2 for clonogenic and invasive activity of androgen-independent prostate cancer cells; suggest a role for ERK regulation of FAK in substrate-dependent survival; and show for the first time, in any cell type, the regulation of FAK expression by ERK signaling pathway.
Subject(s)
Focal Adhesion Protein-Tyrosine Kinases/metabolism , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/pathology , Androgens/metabolism , Anoikis , Cell Line, Tumor , Cell Proliferation , Cell Survival , Enzyme Activation , Humans , MAP Kinase Signaling System , Male , Matrix Metalloproteinase 9/metabolism , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/metabolism , Neoplasm Invasiveness , Phenotype , Phosphorylation , RNA, Small Interfering/metabolism , Tumor Stem Cell AssayABSTRACT
AIMS: This paper reports phase one of a two-part study in a New South Wales area health service, which aimed to evaluate the grading system for clinical nurse consultants. BACKGROUND: Since its inception in 1986, the role and scope of practice of clinical nurse consultants in New South Wales has been viewed with differing expectations leading to role conflict from the nurse consultants themselves and others in health care including managers and other clinicians. METHOD: A quantitative approach was used for this study. A survey comprising of open and closed questions was mailed to all clinical nurse consultants (n = 42) employed in the area. RESULTS: The data presented suggest that ambiguity continues about the role, the scope and the differences within the grading system of clinical nurse consultants. CONCLUSIONS: Clinical nurse consultants need leadership training and support from their managers to fulfil their role. More work is required to clarify the role of clinical nurse consultants.
Subject(s)
Attitude of Health Personnel , Nurse Clinicians/organization & administration , Nurse Clinicians/psychology , Nurse's Role , Professional Autonomy , Career Mobility , Conflict, Psychological , Consultants/psychology , Education, Nursing, Continuing , Health Planning , Health Services Needs and Demand , Humans , Interprofessional Relations , Job Description , Leadership , New South Wales , Nurse Administrators/organization & administration , Nurse Administrators/psychology , Nurse Clinicians/education , Nurse's Role/psychology , Nursing Evaluation Research , Nursing Methodology Research , Nursing Research , Professional Competence , Salaries and Fringe Benefits , Social Support , Surveys and QuestionnairesABSTRACT
New South Wales Health introduced the role of the Clinical Nurse Consultant in 1987. A review of the role was undertaken by an area health service in Western Sydney, NSW, Australia in 1992 and a number of issues were highlighted in the review process, including diverse roles and responsibilities. In 2000, New South Wales Health acknowledged the diversity of roles and developed a grading system based on five domains of practice. This paper reports the second phase of a two-part study that investigated the scope of practice and perceived level of organisational support provided for the Clinical Nurse Consultants in the area health service. Focus group interviews, one for managers and two for nurse consultants, were conducted in order to collect data. Ten Clinical Nurse Consultants, representative of each grade and seven managers, covering various clinical streams, took part in the study. Data were analysed using content analysis and coded using constant comparison and contrast of codes. Results of the study reveal a lack of clarity and understanding of the new grading system. There is an indication that the role is very individual and the incumbents are often overloaded by work and the maze of demands put on them by numerous competing forces. Many of the Clinical Nurse Consultants felt they were working at a grade higher than their position classification. There appears to be a significant need to clarify the roles of each of these members of the health care system and to provide a better reporting scheme.
Subject(s)
Consultants , Job Description , National Health Programs/organization & administration , Nurse Clinicians/organization & administration , Nurse's Role , Attitude of Health Personnel , Female , Humans , Male , Needs Assessment , New South Wales , Nursing Evaluation Research , Quality of Health Care , WorkloadABSTRACT
Recent trends suggest that carcinoma of the prostate is being detected at earlier stages in its natural history; our objective is to determine if this trend is accompanied by changes in tumor characteristics. Two hundred ninety-three men from 1990-1993, 308 from 1994-1996, and 323 from 1998-2000 with newly diagnosed prostate cancer have been evaluated at the University of Colorado Health Sciences Center. We compared the Gleason score, mean age, and the mean prostate-specific antigen (PSA) among the 3 cohorts. The same pathologist reviewed all the pathology slides. A high Gleason prostate cancer score was defined as > or = 7. One hundred seventy-two patients (53.3%) were found to have a high Gleason score in 1998-2000 compared to 116 patients (39.5%) in 1990-1993; the difference was statistically significant (P = 0.0009, Yates-corrected chi2 test). From 1994-1996, 141 patients (45.7%) had a high Gleason score. The mean PSA in high Gleason score, localized prostate cancer was 7.52 ng/mL (range, 0.9-15.3 ng/mL) in the 1998-2000 group, 9.09 ng/mL (range, 1.7-20 ng/mL) in the 1994-1996 group, and 12.6 ng/mL (range, 3.9-25 ng/mL) in the 1990-1993 group. The difference between these groups was statistically significant (P = 0.000018, one-way analysis of variance test). The mean ages for patients in the 3 cohorts were 64.4, 64.5, and 65.2 years of age for the 1998-2000, 1994-1996, and 1990-1993 groups, respectively (P = 0.702). These data suggest a trend toward the diagnosis of more aggressive prostate cancer, with higher Gleason score, and lower PSA in newly diagnosed patients. Continued screening for prostate cancer is resulting in the diagnosis of more unfavorable cancers.