June 8, 2007

Aliquots — Research highlights from VUMC laboratories

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Resurrection of prostate tumors

Normal tissue stem cells gone awry may be at the heart of many types of cancer. Putative cancer stem cells have been identified for several cancer types. In the May 15 issue of Cancer Research, Susan Kasper, Ph.D., and colleagues provide the first direct evidence for the existence of prostate cancer stem/progenitor cells.

The researchers isolated prostate epithelial cells from resected human prostate samples and immortalized them in culture. The clonally derived cell lines, termed “HPET,” expressed embryonic stem cell markers and early progenitor cell markers and retained the ability to differentiate into the three different types of prostate epithelial cells. Most importantly, the HPET cells reconstituted the original prostate tumor — at the same tumor grade — as the tumors from which they were derived.

The authors postulate that the HPET cell lines may provide a model for studying the role of cancer stem cells in tumor progression, metastasis and the development of drug-resistant cancer. Furthermore, they may provide a mechanism for the preclinical testing of novel treatment and/or prevention strategies.

— Melissa Marino

Blood holds clues to bipolar disorder

Since the biological basis of bipolar disorder is uncertain, diagnosis is based solely on the nature and course of symptoms. But a recent study by Christine Konradi, Ph.D., and colleagues suggests that blood cells might hold biomarkers that could aid in the diagnosis and understanding of the disorder.

Previous research suggested that disturbances in mitochondrial energy metabolism in the brain play a role in bipolar disorder. Konradi and colleagues analyzed expression of mitochondrial genes in blood lymphocytes from patients with bipolar disorder and unaffected controls. In response to low-glucose stress — a condition that normally up-regulates the expression of genes involved in mitochondrial energy metabolism — lymphocytes from patients with bipolar disorder showed either no response or a down-regulation of several mitochondrial transcripts.

The results, reported in the May issue of the Archives of General Psychiatry, suggest that the accessibility and manipulability of lymphocytes may prove useful for identifying biomarkers of bipolar disorder and other psychiatric illnesses.

— Melissa Marino

Regulators of pancreas development

The gene Pdx1 is required for both the development of the pancreas and its normal function after birth. Maureen Gannon, Ph.D., and colleagues are working to understand how this critical gene is regulated: what are the genetic sequences in the Pdx1 “promoter” that control its expression, and what protein factors interact with those DNA regions? Perturbations in these factors can lead to defective pancreatic function and diabetes.

In the June issue of Molecular and Cellular Biology, the investigators report that a conserved stretch of DNA called “Area III” in the Pdx1 promoter mediates early pancreas-wide Pdx1 expression. The collaborative team, which included two other “beta cell” laboratories at Vanderbilt (Roland Stein, Ph.D. and Christopher Wright, D.Phil.) and a group in Philadelphia, also demonstrated that Ptf1a, another transcription factor essential for pancreas development, binds to and activates the Pdx1 Area III sequence in the developing mouse pancreas. The study is the first to link these two critical factors genetically and functionally.

— Leigh MacMillan

Salt sways stomach bacteria

Infection with the stomach-dwelling bacterium Helicobacter pylori — particularly with “cag-positive” strains — is a major risk factor for gastric cancer. Environmental factors like high dietary salt intake also influence risk, perhaps in synergy with H. pylori infection, although the mechanisms are poorly understood.

Timothy Cover, M.D., and colleagues investigated how high-salt conditions might influence gene expression in H. pylori strains that contain the cag pathogenicity island, a DNA region that encodes the putative bacterial oncoprotein CagA and the secretory system that delivers CagA into host cells.

In the May 15 issue of Cancer Research, they report that high-salt conditions similar to levels achievable in the human stomach increased the expression of CagA, leading to an increased translocation of CagA into host cells and an enhanced ability of H. pylori to alter gastric epithelial cell morphology and function. The results suggest a mechanism by which a high-salt diet may contribute to increased gastric cancer risk.

— Melissa Marino

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012