Abstract P6-05-04: mRNA expression of PTK6V1 and PTKV2 in human breast cancer

Abstract

Abstract BACKGROUND: Protein tyrosine kinase 6 (PTK6) is an intracellular protein that is upregulated in several human cancers and its localization to the plasma-membrane facilitates its various oncogenic roles in breast cancer cell proliferation, survival, and migration. The full length protein (PTK6V1) and alternative splice variant (PTK6V2) seem to play different roles with the latter being negative regulator of the former. In this study, the level of mRNA expression of PTK6V1 and PTK6V2 were assessed in normal and malignant breast tissue using real time Q-PCR in a cohort of women with breast cancer and correlated to conventional clinico-pathological parameters and clinical outcome. MATERIALS AND METHODS: Breast cancer tissues (n = 127) and normal background tissues (n = 33) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against beta-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analysed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow-up period. RESULTS: The median copy number of transcripts of PTK6V1 were higher in malignant compared with normal breast tissue (23 vs.7) and overall increased with advancing tumour stage (374 vs. 13 for TNM3 vs. TNM1 respectively p=0.019 and 374 vs.23 for TNM3 vs. TNM2 p=0.0244). however these associations did reach statistical significance. PTK6V1 levels were associated with oestrogen receptor (ER) positivity (p = 0.061). The transcript levels were significantly higher in patients who developed recurrence (p=0.03) or died of breast cancer (p=0.003). PTK6V2 transcript levels were generally higher in normal breast tissue than in malignant tissues and decreased with increasing tumour stage and grade however these associations did not reach stastical significance. After a median follow up of 10 years, there was a trend for higher PTK6V2 expression to be associated with longer overall survival (OS) and disease free survival (DFS). PTK6V2/PTK6V1 ratio was a significant predictor of OS. Conclusions Our observations suggest that the two variants of PTK6 play opposing roles in mammary oncogenesis. These findings could have prognostic and therapeutic implications. Citation Format: El Hage Chehade H, Harvey A, Wazir U, Jiang WG, Mokbel K. mRNA expression of PTK6V1 and PTKV2 in human breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-05-04.