The covers an area of nearly 90kbp and contains

The activity of this signaling pathway leads to an
increased mutagenesis, cell cycle progression, and protection against different apoptotic
stresses. Indirect effects of IGF axis depend on interactions between IGFs and other molecules
essential for cancer aetiology (e.g. sex hormones, products if suppressor genes, viruses, other
growth factors) and the style of life (nutrition, physical activity). In oncogenesis of several
6
cancers also the age of the patient remains of crucial importance, which is also reflected by
dysregulation in IGF axis 8-9.
By clinicians, components of IGF system are considered, first of all, as diagnostic
blood and/or tissue biomarkers of cancer, prognostic factors and attractive target of current
anti-tumour therapies. Several mechanisms in which IGF system components act in the
process of carcinogenesis await clarification, mainly due to multifactorial aetiology of the
diseases (lung, skin, breast, prostate, cervix, colorectal, gastric, pancreatic, liver cancers).
Pinpointing of the role played in carcinogenesis by any single signaling pathway remains to
be 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 its
transcription is under the control of two promoters: P1 and P2. It is considered that almost
90% of IGF-I transcripts remain under the control of P1. The P1 human promoter region
consists of 322 nucleotides located in the region of 5’UTR and exon 1 of the regulatory region
in 1630. The most conservative is a 322-nucleotide stretch of 5’UTR. The P1 promoter
sequence requires typical sequences of other genes, such as TATA or CCAAT elements, and
the rest of the area is rich in GC. The P1 promoter has 5 sections protected from DNase
digestion: HS3A, HS3B, HS3C, HS3D, HS3E. The HS3D place is thought to be responsible
for the regulation of IGF-I expression by estrogens 11-12. 5′(CA)n repeats in the P1
promoter region of the IGF-I gene, 1 kb upstream from the transcription site, are a highly
polymorphic microsatellite, comprising a variable length of a cytosine-adenosine (CA) repeat
sequences. The number of CA repeats ranges between 10 to 24 with the most common allele
containing 19 (CA)(192 bp) repeats, characteristic for Caucasians 11-12.