Steroid Biosynthesis and Embryonic Stem Cell Proteins As Putative Predictive Breast Cancer Biomarker

Abstract

Breast cancer is the second most common malignancy in women and is curable if diagnosed early. Sex steroid hormone(reproductive) is known to be involved in the breast cancer. Estrogen and androgen are known to be synthesized in breast carcinoma tissues and estrogen is known to be greatly contributing to the growth of breast carcinoma. Majority of breast cancer tissue express estrogen (ER) receptor,progesterone (PR) and androgen (AR) receptor and the level of expression of these receptors is important factor in prognosis and management of breast cancer. In this study expression of CYP17A, PP2A, CREB3L1, COX-2, and NANOG were investigated for identification of putative predicted biomarker for breast can cer susceptibility.The expression of CYP17A and found to be expressed at around 70-60 kDa. In addition, a variant that has putative stop codon at 239 argine and transcribes 28 kDa protein was found. This is the first report for such allelic variant in breast cancer tissue. Most of the samples were heterozygous to this. Furthermore, it was found for the first time putative alternative transcript which is transcribed around 128 aminoacid downstream to first methionine of normal transcript, and gives around 37 kDa protein.PP2A is a regulatory protein that regulates the expression of steroidogenic genes.Expression of PP2A was looked into and found that the regulatory subunit is expressed in most of the samples. However, catalytic subunit to be expressed only in71% of the samples indicating its regulatoryrole in expression of steroidogenic genes.In addition, expression of CREB3L1, a CREB/ATF family transcription factor protein expressed in endoplasmic reticulum stress was observed. This is the first report for the expression of CREB3L1 in breast cancer. In addition, putative splicing variants of around 38 kDa and 20 kDa was observed. However the role of this protein in breast cancer from the present study was not explained but speculation was made that this protein might be involved in expression of protooncogene, or might have been involved in expression of variants of CYP17A and COX-2 among the proteins studied.COX-2 expression and CYP19 (aromatase) expression has been found to be correlated in breast cancer. Aromatase is involved in biosynthesis of estrogen, and estrogen has been found to be correlated with breast cancer. High expression of putative splicing variant of COX-2 was observed. In addition, it was found expression of COX-2 variants of 35 kDa and 25 kDa which could have been expressed from same gene by induction through signaling pathway. This is the first report indicating presence of putative COX-2 variants in human.In order to clarify whether breast cancer tissue has pleopotency, expression of Embryonic Stem cell protein NANOG was looked.Expression of NANOG in breast cancer tissue was found. In addition, additional variant of 20 kDa that corresponds to the molecular size of Developmental pluripotency associated protein 3, which is also homeobox domain protein homolog of NANOG was found. This is in concordance to other reports that has reported expression of NANOG in breast cancer.