The activity of this signaling pathway leads to anincreased mutagenesis, cell cycle progression, and protection against different apoptoticstresses. Indirect effects of IGF axis depend on interactions between IGFs and other moleculesessential for cancer aetiology (e.g. sex hormones, products if suppressor genes, viruses, othergrowth factors) and the style of life (nutrition, physical activity). In oncogenesis of several 6cancers also the age of the patient remains of crucial importance, which is also reflected bydysregulation in IGF axis 8-9.By clinicians, components of IGF system are considered, first of all, as diagnosticblood and/or tissue biomarkers of cancer, prognostic factors and attractive target of currentanti-tumour therapies.
Several mechanisms in which IGF system components act in theprocess of carcinogenesis await clarification, mainly due to multifactorial aetiology of thediseases (lung, skin, breast, prostate, cervix, colorectal, gastric, pancreatic, liver cancers).Pinpointing of the role played in carcinogenesis by any single signaling pathway remains tobe particularly difficult 6, 10.Gene coding the human protein IGF-1, placed in the long arm of chromosome 12(12q22-24.1), covers an area of nearly 90kbp and contains six exons separated by very long(1.
9-50kbp) introns. The sequence of the IGF-1 gene is most conservative, and itstranscription is under the control of two promoters: P1 and P2. It is considered that almost90% of IGF-I transcripts remain under the control of P1.
The P1 human promoter regionconsists of 322 nucleotides located in the region of 5’UTR and exon 1 of the regulatory regionin 1630. The most conservative is a 322-nucleotide stretch of 5’UTR. The P1 promotersequence requires typical sequences of other genes, such as TATA or CCAAT elements, andthe rest of the area is rich in GC. The P1 promoter has 5 sections protected from DNasedigestion: HS3A, HS3B, HS3C, HS3D, HS3E. The HS3D place is thought to be responsiblefor the regulation of IGF-I expression by estrogens 11-12. 5′(CA)n repeats in the P1promoter region of the IGF-I gene, 1 kb upstream from the transcription site, are a highlypolymorphic microsatellite, comprising a variable length of a cytosine-adenosine (CA) repeatsequences.
The number of CA repeats ranges between 10 to 24 with the most common allelecontaining 19 (CA)(192 bp) repeats, characteristic for Caucasians 11-12.