Cancer has been with us since we became human, and probably before, since cancer isn’t common to our species. In a fundamental way, cancer is us. Cancer was once healthy tissue, starting out as a cell in your body fulfilling its function to keep the collective whole, you, functioning. This cell toed the line, divided when it was supposed to, stopped dividing when it was supposed to, differentiated and specialized to perform its function, and if it had remained normal, it might have died when told to do so after that function was fulfilled. Those are three of the hallmarks of cancer: uncontrolled cell division (cells making more cells), failure to respond to the normal programs that put the brakes on cell division, and failure to undergo programmed cell death (die when the time is right).
The process by which a normal cell becomes cancerous is called malignant transformation or carcinogenesis. This video provides an excellent overview of the process.
To understand how cancer forms, we need a basic framework for understanding cellular function and its regulation at the molecular level. Don’t get bogged down in the terms. Cellular function refers to how the cell does its programmed job, how it grows and divides, and how it dies, the same basic life cycle that the human host experiences. Regulation at the molecular level means the plan the cell follows, the blueprint for its growth, function, and death. It starts with DNA, the double helix genetic blueprint in all cells that contains the instructions for the cell’s functions and life plan.
So what does DNA actually do, or perhaps the better question, how does the information encoded in DNA actually instruct the cell what to do? This gets into something call the Central Dogma of Molecular Biology. That’s a fancy title for the way in which the instructions encoded in DNA are used to manufacture proteins, the work horses of cells. Now, when most people think about proteins, they envision a juicy piece of meat or powerful muscles, and the components used to build muscle fibers are proteins. But proteins are much more than that. They are the essential building blocks of cells, which in turn build tissues, organs, and all parts of the body. They can be structural, like the fibers that form the cell’s cytoskeleton and histone proteins that wrap around DNA strands and protect them. They can be functional, forming enzymes that do everything from metabolize nutrients, breaking them down into usable building blocks for building biomass and generating energy for the cell. They also play a critical role in transmitting information within cells and between cells, integrating communication between different parts of the body.
Proteins are made up of chains of amino acids, and the order in which they are put together is determined by the sequence of the portion of DNA that encodes that protein. That sequence is called a gene. But as a matter of practicality, since DNA is housed in a subcellular organelle called the nucleus and therefore inaccessible to the protein production machinery in the cytoplasm, and because the cell needs to protect the integrity of its DNA, proteins are not built using pieces of actual DNA. The portion of the DNA, the gene, that encodes instructions for making a specific protein, is first transcribed into an intermediate molecule, call messenger RNA. Transcriptional machinery within the nucleus unwinds and separates the DNA strands, using one strand to copy the information necessary to build a protein. The messenger RNA molecule is then transported out of the nucleus and used by the protein synthesis machinery to translate the information encoded by the mRNA to protein. That’s the Central Dogma: DNA transcribed to RNA, and RNA translated to protein.
The abnormal growth that is cancer is controlled by abnormal proteins that were once (supposed to be) normal proteins. Most of the proteins that drive cancer are proteins that regulate cellular division and cellular survival, and they fall into two basic categories: oncoproteins and tumor suppressors. Oncoproteins are hyperactive proteins that start out as normal proteins, encoded by normal genes, proto-oncogenes. They become oncogenes due to alterations in DNA: mutations that change the DNA sequence, which in turn changes the amino acid encoded and the function of the protein; DNA repair mistakes that cause multiple copies of genes (amplification) to produce too much of a protein that drives growth and survival; changes in DNA that make the gene more accessible, which in turn causes the cell to make more copies of the encoded protein. DNA damage that causes breaks, which can eliminate genes that normally keep cell growth controlled, can silence tumor suppressors.
What’s worse is that the longer the cancer grows unchecked, the more mutations and DNA changes it collects. Those alterations and mutations that give the cell an advantage (more growth, better survival, the ability to break away from the tumor mass and spread) make the cancer more aggressive and difficult to treat.
In my next post, I’ll cover the process of malignant transformation of breast cells, which leads to breast cancer.