Breast carcinoma, one of the most frequent malignancies in women, is a complex disease in which a
number of different factors combine to drive pathogenesis.
The biopathological characterization of these tumors is essential to determine their aggressiveness
and to find the most appropriate therapy.
As in others neoplasms, the deregulation of signal transduction pathways is frequently responsible
for conferring selective biological advantages to the tumor.
Phosphoinositides play an essential role in diverse cellular functions, their metabolism is highly
active, and is tightly controlled. Among the enzymes implicated in this pathway, phospholipase C
beta 1 (PLCβ1) is one of the key regulators, both at the cytoplasmic and the nuclear level.
The PLCβ1 gene maps onto the short arm of chromosome 20, a region that has been shown to be
altered in several solid tumors, including breast cancer.
In the present study a FISH approach was used to investigate the genetic alterations of the PLCβ1
gene in various classes of breast cancer which differ in their invasiveness and proliferation status,
according to their mitotic index. The overall aim was to find out whether this enzyme could be a
suitable prognostic marker for this neoplasm.
Our results show that 83% of cases had aneusomies at the 20p12 level, and the most frequent
alteration is a gain in this specific locus. Indeed, we found that this amplification is not related to
the invasion status since there were no differences in amplified tumor frequencies between in situ
and invasive breast cancer. On the contrary, the gain of PLCβ1 was significantly related to the
mitotic index (p = 0.001).
To verify if the change in genetic dosage influences the expression of PLCβ1 we performed Real
Time PCR and Immunohystochemical analysis. Our results confirmed that amplified tumors have
higher levels of PLCβ1 mRNA, which is the sum of the two splicing isoforms 1a and 1b.
On the other hand, even if protein levels were higher in the majority of cases compared to the nontumoral
specimens, there were no significant associations between gain and overexpression.
Finally, the significant association between the amplification of PLCβ1 and others important
clinicopathological parameters, such as grading and hormonal receptors status, confirmed a
correlation of this enzyme with the aggressiveness of breast cancer. This suggests that PLCβ1 has
the potential to be a prognostic marker in these tumors. However, further work needs to be carried
out to validate these preliminary findings.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:1077 |
| Date | 26 May 2008 |
| Creators | Molinari, Chiara <1978> |
| Contributors | Cocco, Lucio Ildebrando |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | Italian |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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