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You want to find out why apoptosis fails to occur in several cell lines derived

ID: 70934 • Letter: Y

Question

You want to find out why apoptosis fails to occur in several cell lines derived from tumors. To identify differences between the tumor cell lines (T1, T2, and T3) and a control cell line (C) that might prevent tumor cells from undergoing normal apoptosis, you isolate proteins from cells that have (+) or have not (–) been treated to induce apoptosis. You load the protein samples on gels and perform immunoblotting with antibodies against proteins involved in apoptosis. Confusingly, several proteins have altered levels or altered apparent sizes in the tumor cell lines, as shown in the figure below. Suggest a hypothesis for each tumor cell line to explain its apoptosis defect and the immunoblots.

C T1 C T2 C T3 FAS death receptor nuclear lamins caspase-9 FADD BH3-only protein AP protein Q18.02

Explanation / Answer

The programmed cell death is called apoptosis. Apoptosis and necrosis are the two processes through which cell meets death, which are controlled by numerous cell signals. Apoptosis is the most typical form of cell death that is operated by a series of events controlled by genes (programmed cell death). The cellular fragments of an apoptotic cell are ingested by the surrounding cells.

The caspases, FAS death receptor and IAP proteins are mainly responsible for occurrence of apoptosis. The tumor cells usually have the mechanism to escape from apoptosis, so the above stated proteins do not express in tumor cells, even they are induced.

In immunoblots (A) C (+) cells expresses Caspase-9 and BH3-only protein due to induction. However, even in an induced condition, these proteins do not express in T1 cells. In immunoblots (B), the FAS death receptor expresses equally in both untreated and induced tumor cells, but express low amount of Fas-Associated protein with Death Domain (FADD) to escape form apoptosis. In immunoblots (C) The control induced cells have degraded nuclear laminas due to apoptosis. But the tumor cells expressing equal amount.    

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