ABSTRACT
OBJECTIVE: Association between prostate cancer and obesity remains controversial. Allelic deletions of PTEN, a tumor suppressor gene, are common in prostate cancer in men. Monoallelic Pten deletion in mice causes low prostatic intraepithelial neoplasia (mPIN). This study tested the effect of a hypercaloric diet on prostate cancer in Pten (+/-) mice. METHODS: 1-month old mice were fed a high-calorie diet deriving 45% calories from fat for 3 and 6 months before prostate was analyzed histologically and biochemically for mPIN progression. Because Pten (+/-) mice are protected against diet-induced insulin resistance, we tested the role of insulin on cell growth in RWPE-1 normal human prostatic epithelial cells with siRNA knockdown of PTEN. RESULTS: In addition to activating PI3 kinase/Akt and Ras/MAPkinase pathways, high-calorie diet causes neoplastic progression, angiogenesis, inflammation and epithelial-mesenchymal transition. It also elevates the expression of fatty acid synthase (FAS), a lipogenic gene commonly elevated in progressive cancer. SiRNA-mediated downregulation of PTEN demonstrates increased cell growth and motility, and soft agar clonicity in addition to elevation in FAS in response to insulin in RWPE-1 normal human prostatic cells. Downregulating FAS in addition to PTEN, blunted the proliferative effect of insulin (and IL-6) in RWPE-1 cells. CONCLUSION: High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Muir-Torre Syndrome/diagnosis , Muir-Torre Syndrome/pathology , Skin/pathology , Aged , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Female , Humans , Male , Middle Aged , Muir-Torre Syndrome/genetics , MutS Homolog 2 Protein/genetics , Mutation/geneticsABSTRACT
BACKGROUND: Despite early detection having been identified as a key factor in long-term survival of patients with breast cancer, women with locally advanced breast cancer continued to present at many medical centers. METHODS: Women with locally advanced breast cancer (LABC) (N = 11) and matched controls (N = 11) with Stage I or II breast cancer completed semi-structured interviews and the Hospital Anxiety and Depression Scale, Life Orientation Test, Multidimensional Health Locus of Control Scale, Body Investment Scale, Monitor-Blunter Style Scale, and Religious Coping Scale. Five spouses of the LABC group and eight control partners were similarly assessed. RESULTS: On psychological tests, no significant differences were found between patient groups; however, LABC spouses reported significantly greater active religious surrender (t = 2.37, P = 0.037) and depression (t = 3.54, P = 0.047) than control spouses. The women's semi-structured interviews identified that LABC was associated with inattention to routine breast cancer screening, denial, fatalism and reliance on alternative therapies. Spouses of the LABC group tended to be more passive in their wives' medical care, and also utilized fatalistic thinking and denial. CONCLUSIONS: It is important for health care providers to identify patients who will require extra encouragement to seek timely medical care and to follow through with treatment recommendations.
