Expression of CCND1, P16 and CDK6 in Human Basal Cell Carcinoma
Basal cell carcinoma (BCC) is the most common cancer among skin cancers. The incidence of cutaneous malignant melanoma (CMM) and non-melanoma skin cancer (NMSC) has increased more than 600% worldwide since the 1940s. Carcinogenesis is a multi-step process involving multiple genetic alterations. T...
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| Main Author: | |
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| Format: | Thesis |
| Language: | English English |
| Published: |
2007
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/7128/1/FPSK%28M%29_2007_17a.pdf |
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| Summary: | Basal cell carcinoma (BCC) is the most common cancer among skin cancers. The
incidence of cutaneous malignant melanoma (CMM) and non-melanoma skin cancer
(NMSC) has increased more than 600% worldwide since the 1940s. Carcinogenesis is a
multi-step process involving multiple genetic alterations. The connection between cell
cycle proliferation and cancer resulting in deregulated cellular proliferation leads to
cancer. Cancer has been associated with disturbances in cell cycle regulation. Recent
studies have shown that p16, CDK6 and CCND1 mRNA genes and protein expression are
involved in the tumorgenesis of skin cancer. These genes play a role in cell cycle
proliferation. In this study, we assessed the expression of a cyclin, a cyclin dependent
kinase, and a cyclin kinase inhibitor in skin BCC tissue. Reverse Transcription in situ
polymerase chain reaction (RT in situ PCR) and immunohistochemistry (IHC) were used
to detect the expression of p16, CDK6 and CCND1 mRNA genes through them of protein
expression in human skin BCC tissue The results show that p16, CDK6 and CCND1 mRNA genes and protein are expressed in
both normal and human skin BCC tissues. CCND1, CDK6 and p16 mRNA can be found
to be expressed mostly in cytoplasm. The mRNA expression in BCC is higher than
normal skin tissue. Protein expression of CCND1 and p16 in different BCC tissue are
greater than normal skin tissue. p16 mRNA and protein expression is stronger than other
genes. RT in situ PCR and IHC analysis data showed significant expression of CCND1,
p16 mRNA and protein in BCC compared to normal skin tissue (p<0.05%).
Investigation on Iranian samples showed the protein expression of CDK6 is not
significant (p>0.05%) but the expression of mRNA for CDK6 gene is significant
(p<0.05%). The findings of IHC study on tissue microarray (TMA) demonstrated
significant protein expression of p16 and CCND1 genes (p<0.05%) which support
findings on Iranian samples. Taken together, these data provide evidence that cell cycle
deregulation in G1-phase is a critical event during the course of carcinogenesis of BCC.
In conclusion, this study showed that p16, CDK6 and CCND1 are involved in the process
of tumorgenesis in human BCC. p16, CDK6 and CCND1 mRNA genes are expressed to
induce cell cycle proliferation and also the protein expression of these genes can
influence proliferation of the cell cycle. RT in situ PCR study on ten Iranian samples
illustrated significant expression of p16 (p=0.026), CDK6 (p=0.015) and CCND1
(p=0.021) mRNA genes (p<0.05%). There is a direct correlation between p16 and
CCND1 and also between p16 and CDK6. There is no correlation between CCND1 and
CDK6. IHC analysis on the Iranian samples demonstrated significant protein expression
of p16 (p=0.019) and CCND1 (p=0.021) (p<0.05%) but CDK6 protein expression is not
significant (p=0.082). Direct correlation between p16 and CCND1 was obtained. TMA samples were used for the IHC study only for p16 (p=0.008) and CCND1 (p=0.024) due
to insufficient tissue to perform complete study with IHC. Even CDK6 could not be done
because of insufficient samples then the result of TMA samples using IHC supports the
findings on the Iranian samples about protein expression of CCND1 and p16 genes. RT
in situ PCR is a sensitive method to study specific mRNA genes. However there are
problems in getting good results as well as their interpretation. IHC on the other hand
shows more reliable results. These methods may be used in the clinical setting and as it
can be used to predict tumor behavior including cellular proliferation which can affect
the mode of therapy. |
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