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Aliquots ó research highlights from VUMC laboratories

4/15/2010 -  

Dose up on Neurog3 to make insulin

The protein Neurog3 is essential for the development of hormone-secreting islet cells in the pancreas. Understanding Neurog3’s expression and function is key for strategies aimed at converting embryonic stem cells or pancreatic cells into insulin-producing beta cells for diabetes treatments.

Guoqiang Gu, Ph.D., and colleagues used genetically altered mouse models to reduce Neurog3 expression levels in pancreatic endocrine progenitor cells – cells that will mature into hormone-secreting cells – without altering its distribution. Lowered Neurog3 expression reduced the overall production of endocrine islet cells, but did not affect the proportions of the various islet cells that formed. Reduced Neurog3 also activated expression of Neurog3 in other pancreatic epithelial cells, but those cells did not mature into endocrine cells, possibly because the Neurog3 levels were too low.

The findings in the March 1 issue of Developmental Biology demonstrate that high levels of Neurog3 are critical for the commitment of multipotent pancreatic progenitor cells (cells capable of maturing into multiple cell types) to an endocrine cell fate.

Leigh MacMillan

 

FISHing out lung cancer

Diagnosing lung cancer from bronchoscopy specimens can be difficult using standard microscopic examination of cells (cytology) – in part due to the small amount of specimen that can be collected.

In bronchial brushing specimens from a clinical population, Otis Rickman, D.O., and colleagues evaluated the use of fluorescence in situ hybridization (FISH) – which tags cells with chromosomal abnormalities often seen in cancer – as an adjunct to routine cytology.

In the March 1 issue of the American Journal of Respiratory and Critical Care Medicine, they report that FISH was able to detect an additional 32 percent of lung cancers that were missed by routine cytology. FISH was especially useful for peripheral nodules, detecting an additional 28 percent (tumors greater than 2 cm) to 44 percent (tumors less than 2 cm) of lung cancers. The results suggest that, used in conjunction with routine cytology, FISH testing – which can be performed on specimens with few tumor cells present – can improve lung cancer detection, especially in peripheral lung nodules.

Melissa Marino

 

Tool helps mine for cancer variations

Understanding how cancer develops and progresses is becoming increasingly dependent on making sense out of the mountains of genomic and proteomic data being generated and compiled in public databases. Several genomic and proteomic databases exist, but differ in variation and disease types, and in scope (genome-wide vs. single gene).

Bing Zhang, Ph.D., Jing Li, Ph.D., and colleagues developed an integrated database – called the Cancer Proteome Variation Database (CanProVar) – by compiling known protein sequence variations (with a focus on cancer-related variations) from these various public sources. As reported in the March issue of Human Mutation, CanProVar contains 8,570 cancer-related variations in 2,921 proteins – and 41,541 non-cancer specific variations in 30,322 proteins. They also show that the database can help reveal functional characteristics of cancer-related variations and proteins bearing these variations.

The authors suggest that CanProVar can serve “as a bridge between genomic data and proteomic studies” for identifying cancer-causative mutations or cancer biomarkers. The database can be accessed at: http://bioinfo.vanderbilt.edu/canprovar.

Melissa Marino

 

Molecular motors in the gut

Wellcome Images

Wellcome Images

The cells lining the small intestines are studded with microvilli – finger-like protrusions that form a “brush border” and increase the capacity for nutrient handling. Inside each microvillus, the motor protein myosin-1a (Myo1a) links a structural actin protein core to the cell surface. Mice missing Myo1a have defects in the brush border, but they don’t have any obvious physiological defects, suggesting that another myosin might compensate for Myo1a’s absence.

Matthew Tyska, Ph.D., and colleagues used a proteomic approach to compare the myosin proteins in brush borders from normal and Myo1a-knockout mice. They found that normal brush borders also contain Myo1d, and that it is concentrated at the bases and tips of the microvilli. When Myo1a is absent, Myo1d levels increase two-fold, and the protein redistributes along the length of the microvilli. The findings in the March 15 Molecular Biology of the Cell support a role for Myo1d in normal brush border physiology and suggest that this myosin steps in when Myo1a is missing.

Leigh MacMillan

 

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.

 

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
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