Our analysis of published information showed that decrease PTEN mRNA levels in BLCs compared with usual samples, suggesting reduce PTEN protein ranges in BLCs compared with usual tissues. We examined the expression of stathmin, which has recently been proven to be overexpressed in reduced PTEN expressing breast cancers. In accordance with these published observations, stathmin protein was overexpressed in BLCs compared with HER2 carcinomas. Stathmin for that reason represents a potential marker for PTEN dependent PI3K pathway activation. Altogether, tran scriptomic and proteomic analyses highlighted lower expression of PTEN in BLCs. Genomic alterations in the PTEN tumour suppressor gene in basal like breast cancer We then examined no matter whether variations in PTEN protein expres sion could come up from genomic alterations in our BLC popula tion.
Genomic DNA isolated from tumours was analysed on SNP arrays. The 2 populations behaved in a different way for PTEN DNA copy number inside a important method. In contrast on the entire HER2 population exhibiting normal PTEN CN, reduction of PTEN CN was observed in 46. 1% BLCs. Of note selleck chemicals is our BLC population integrated 1 BRCA1 tumour which also presented a reduction of PTEN CN. We observed the only double deletion in the PTEN gene was observed inside a BLC patient having a regular status of BRCA1 with the exception from the c. 4039A G polymorphism. We also observed a obtain of PTEN CN in two of 13 BLCs but these two tumours expressed PTEN protein at a level similar to that 1 in BLCs with regular PTEN CN. Importantly, PTEN CN correlated with PTEN protein level in a important manner from the total population.
buy CHIR-99021 These final results suggest that genomic alterations on the PTEN locus are straight responsible for minimal PTEN protein expression in about 50% of BLCs. Lower PTEN pro tein expression inside the other half of BLCs may result from PTEN promoter methylation and or PTEN mutation. Despite the fact that coding mutations of PTEN have been thought for being unusual in breast cancer, PTEN nucleotide sequence mutations have just lately been detected exclusively in PTEN null non hereditary breast can cer. Nonetheless, we didn’t detect any PTEN mutation in our series of 13 BLCs, in agreement using a current report showing the uncommon PTEN mutations observed in breast cancer have been limited to hormone receptor favourable carcinomas. Hence, very low PTEN protein expres sion in the 50% BLCs without any PTEN CN loss may perhaps come up from epigenetic modifications. In addition, by analysing a public information set generated from 42 BLCs and 32 hormone receptors beneficial luminal A breast carcinomas, we also found a reduction of PTEN CN, largely in BLCs, and a correlation in between PTEN CN and PTEN mRNA in the complete population.