Question

2. You have learned MANY different mechanisms that can lead to cancer development. One of these mechanisms involves changes in epigenetics during tumor initiation and progression.

A. HDAC proteins (a class of eraser proteins) are often overexpressed in cancer cells. Provide a 2-4 sentence explanation for how HDAC overexpression could promote tumor growth (include what the abbreviation HDAC stands for).

B. If HDAC overexpression favors tumor initiation, explain one potential problem of HDAC underexpression that could result in tumor growth.

C. A few anti-cancer drugs are currently on the market that inhibit HDACs. Given what you know about HDACs and cancer, provide a brief molecular explanation about how these drugs may work. Would you anticipate there to be any side effects? If so, provide an example with a brief explanation.

Answer 1

Epigenetic modifications: These modifications alter the recruitment of RNA polymerase to the gene locus by changing the compactness of the chromatin. Ex: Histone modifications and DNA methylation.

Histones are positively charged basic proteins that bind to negatively charged DNA. Factors that alter the charge on histones alter the compactness of the chromatin.

HAT = Histone acetyltransferase. These proteins acetylate histones and reduce the compactness of the chromatin.

HDAC = Histone deacetylase. These proteins remove acetyl groups from histones and increase the compactness of the chromatin.

Histone methylases = Increase the compactness of the chromatin

Histone demethylases = Decrease the compactness of the chromatin

A. HADCs deacetylate histone proteins and help in establishing heterochromatin state. Overexpression of HDACs may result in tumor formation if HDAC acts on a tumor suppressor gene such as p53, its expression would be reduced. This leads to increased cell proliferation and cancer.

B. Under-expression of HDACs may result in tumor formation if HDAC acts on a protooncogene. Its expression would be increased. This leads to increased cell proliferation and cancer.

C. Drugs that target HDACs regulate the abnormal function of these proteins so that proper gene regulation status is established.

Yes. There would be side effects as HDAcs are general epigenetic factors involved in the regulation of genes involved in other pathways as well.