AAC-11 Newly Linked to Cervical Cancer

Introduction
Researchers have found a new genetic link to the development of metastatic cervical cancer. This article discusses how the overexpression of the gene AAC-11 leads to the production of other proteins that induce anti-apoptosis effects in the cell. The researchers found that levels of expression of AAC-11 were low in normal cervical tissue as well as cervical tissue that is in the early stages of becoming cancerous. The levels of AAC-11 increased by 200 to 400% in cervical cancer that had invaded regional lymph nodes or became metastatic (1). This indicates that AAC-11 is not the primary mutation that leads to the development of cervical cancer; rather, it is a mutation that occurs after the cancer develops but aids the progression by inhibiting apoptosis.


The Raw Data

 This graph demonstrates the increased survival in the cells that over-express the AAC-11 gene, denoted in the figure as "AAC-11." The cells over-expressing this gene were able to survive about two times longer than normal cells, "wild type" and cells treated with just the vector used to transfer the AAC-11, denoted as "pCR3-Uni." This indicates that the cells expressing high levels of AAC-11 are able to evade apoptosis either by ignoring the environmental signals to undergo apoptosis, or by constantly producing signals to proliferate, regardless of the environment. Both of these processes are linked to molecules controlled by the transcription of AAC-11.

The figure at the right measures the concentration of each protein. Lane 3 represents the cells that over-express AAC-11 while lanes 1 and 2 are both controls. It is shown that in cells with high levels of AAC-11, MMP-2 and MT1-MMP are both over-expressed while TIMP-2 is down-regulated. MMP's are a class of proteins that are involved in the cleavage of cell-surface receptors, indicating that they could be involved in reducing the response to apoptotic signals by eliminating the receptors that would normally respond to these signals. TIMP is a protein that deactivates MMP's. Therefore, when TIMP is not expressed, MMP's are able to cleave cell surface receptors without any regulation (2). The research team claimed that the levels of Beta-actin were elevated in cells that expressed high levels of AAC-11 as well. However, I do not see any significant difference in the expression of Beta-actin in the figure, nor in any other test that was performed by the team. It would be logical if Beta-actin were expressed in higher concentrations in these cancerous cells because it is involved in the up-regulation of DNA transcription which is necessary in cancerous cells.

Conclusion
The over-expression of AAC-11 clearly leads to increased MMP levels as well as decreased TIMP levels. Together, these 2 events could lead to resistance to apoptosis because the cell would no longer receive extra-cellular signals which would tell it to either undergo apoptosis or stop proliferation. I find it interesting that AAC-11 was expressed at normal levels in the primary stages of cancer, because I would think that the cell would need to resist apoptosis signals throughout the entire pathway to becoming cancerous. However, I do believe that the protein products of this gene would be viable targets for drugs that would be designed to inhibit that metastasis of already confirmed cervical cancer.


References
1. Kim, Jin Woo, Hyun Suk Cho, Jeong Hyun Kim, Soo Young Hur, Tae Eung Kim, Joon Mo Lee, In-Kyung Kim, and Sung Eun Namkoong. "AAC-11 Overexpression Induces Invasion and Protects Cervical Cancer Cells from Apoptosis." Laboratory Investigation (n.d.): n. pag. Web. 3 June 2014.

2. Nagase, Hideaki, Robert Visse, and Gillian Murphy. "Structure and Function of Matirix Metalloproteinases and TIMPs." Cardiovascular Research (2006): n. pag. Web