The tumor etiology and pathogenesis
Cause of cancer research caused by the tumor initiating factor, tumor incidence of school are working on the pathogenesis of cancer and tumors. To cure the tumor and the tumor to prevent the occurrence of the key issues is to identify the cause of the tumor and its pathogenesis.

The tumor on the etiology and pathogenesis for many years conducted extensive research, although not yet entirely clear, but in recent years, the rapid development of molecular biology, especially for cancer genes and tumor suppressor gene research has revealed a preliminary Some cause cancer incidence and mechanisms, such as Burkitt lymphoma and human T-cell leukemia / lymphoma. The current study showed that the tumor is essentially genetic disease. Cause damage to genetic material DNA (mutations) in a variety of environmental and genetic factors may be carcinogenic to the concerted or sequential manner, activation of oncogenes or (and) inactivation of tumor suppressor genes, into cells so that the (transformation) . The cells can be transformed were polyclonal first hyperplasia, after a lengthy multi-stage evolution (progression), one of the clones may be relatively unlimited expansion through additional mutations, the selective formation of the different characteristics of the subcloning (Heterogeneity), which was the ability of invasion and metastasis (malignant transformation), the formation of malignant tumors. Figure 7-19 show cause tumors and pathogenesis model.

 

Figure 7-19 and the cause of tumor pathogenesis model (taken from Kumar, a little change)

First, the tumor molecular biology-based

1. Oncogene

(1) proto-oncogene, cancer genes and their products: modern molecular biology is one of the major achievements of the discovery of proto-oncogenes (proto-oncogene) and has a proto-oncogene into cancer-causing oncogene (oncogene) the ability of . Bishop and Varmus in this regard because of the contributions received the Nobel Prize in 1989.

Oncogene is the first in-retroviral (RNA virus) found. To contain the virus retroviral oncogene can be rapidly induced tumors in animals and in vitro cell transformation. Later in the DNA of normal cells are also found with the virus oncogene almost identical DNA sequence. Cells, known as oncogenes. Such as ras, myc, and so on. As the gene in cancer cells and normal cells based on non-activated form, it is also known as the proto-oncogene. Proto-oncogene may be due to many factors role in its structure change, and become activated oncogene.

Proto-oncogene encoded protein is the most important normal cell growth and cell growth factor growth factor receptor, such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor receptor (EGF -R), an important signal transduction protein (such as tyrosine kinase, ammonia-wire - threonine kinase, etc.), as well as nuclear regulatory proteins (such as transcription activation protein). Table 7-4 show common cancer genes and their products.

Table 7-4 of several common cancer and ways to activate genes and their related human tumor

Encoded protein
  Proto-oncogene
  Activation mechanism
  Related to human tumor
 
Growth factor:
 
PDGF-β chain
  sis
  Over-expression
  Astrocytoma, osteosarcoma
 
FGF
  hst-1, int-2
  Over-expression
  Stomach cancer, bladder cancer, breast cancer
 
Growth factor receptor:
 
EGF receptor
  erb-B1
  Amplification
  Glioma
 
EGF-like receptor
  neu (erb-B2)
  Amplification
  Breast cancer, ovarian cancer, renal cell carcinoma
 
Signal transduction protein:
 
GTP-binding protein
  ras
  Mutation
  A variety of human tumors, including lung, colon, pancreas, leukemia
 
Tyrosine kinase
  abl
  Translocation
  Chronic myelogenous, acute lymphoblastic leukemia
 
Nuclear regulatory proteins:
 
Transcription activator protein
  myc
  Translocation
  Burkitt lymphoma
 
N-myc
  Amplification
  Neuroblastoma, small cell lung cancer
 
Mitochondrial protein:
  bcl-2
  Translocation
  Follicular B-cell lymphoma
 
 

(Taken from Basic Pathology; 1992)

(2) proto-oncogene activation: proto-oncogene in a variety of environmental or genetic factors, structural change (mutation) and a cancer gene; it could be a proto-oncogene structure itself has not changed, but As the regulation of oncogene expression of the gene changed so that over-expression of proto-oncogene. Above the level of gene changes may lead to further stimulate cell growth or sustained over the signals, so that the cells transformed. Proto-oncogene mutation caused by the change in the structure of DNA, including point mutation (90% of pancreatic cancer as a point mutation in the ras gene), chromosomal translocation (such as Burkitt's lymphoma t (8:14), chronic myeloid leukemia Phl chromosome), the insertion mutagenesis, gene deletion and gene amplification (such as neuroblastoma of the N-myc proto-oncogene can be copied into as many as several hundred copies of the cells showed chromosome genetics on the double minor and Into all areas). Cancer gene-encoded protein (protein cancer) and the proto-oncogene product similar to the normal, but there are differences in the quality or quantity. Through the growth factor or growth factor receptor, have a mutation of the signal transduction protein and DNA binding of transcription factors such as the mechanism to adjust its target protein in cancer cell metabolism, cell to the gradual transformation into tumor cells.