Abstract 377: Organic Anion Transporting Polypeptides (OATPs): A potential new molecular target for imaging/therapy of hormone dependent breast cancers
Bibliographic record
Abstract
Abstract The purpose of this research is to explore the potential of Organic Anion Transporting Polypeptides (OATPs), a family of membrane-associated uptake transporters, as a novel molecular target for imaging and treatment of breast cancers. It has been reported that some of the OATP isoforms (e.g. OATP1A2, OATP2B1) are over expressed (up to ten times) in breast cancer tissues as compared to surrounding normal tissues. Furthermore, estrone-3-sulpahte (E3S), a predominant source for tumour estrogen in post-menopausal patients with hormone dependent breast cancers has been characterized to be a substrate for many of the OATP isoforms. This suggests that the two- three times higher E3S concentration reported in malignant tissues, as compared to the surrounding normal tissues, could be due to higher expression and/or increased functional activity of OATPs in breast tumour tissues. By characterizing the differential expression and function of OATPs in breast epithelial cells and breast cancer cells, their potential as novel molecular targets can be established. In this study, the gene and protein expression of seven OATPs (i.e. OATP1A2, OATP1B1, OATP1B3, OATP1C1, OATP2B1, OATP3A1 and OATP4A1) that are known to recognize E3S as a substrate, were compared in normal breast epithelial cells (MCF10A), hormone dependent breast cancer cells (MCF7) and hormone independent breast cancer cells (MDA/LCC6-435, MDA-MB-231 and MDA-MB-468) by real time qPCR and immunoblotting. OATP mediated E3S uptake was also characterized by transport experiments. Six of the seven OATPs (except SLCO1C1) were found to be expressed in breast cancer cells at the transcript level. Expression of SLCO1A2, 1B1, 1B3, 2B1 and 3A1 was exclusive, similar or significantly higher (p<0.001) in cancer cell lines compared to the normal breast epithelial cells (MCF10A). At the protein level, expression of all the OATP isoforms was observed to be either exclusive or higher in the cancer cell lines as compared to the MCF10A cells. Specificity of OATP mediated E3S uptake was observed only in the cancer cells with significantly higher total uptake in the MCF7 cells. Estimation of the transport kinetics (Km and Vmax) of E3S uptake by the breast cancer cell lines, demonstrated E3S transport efficiency to be 10 times greater in the hormone dependent breast cancer cells than in the hormone independent cells. Taken together, these data suggest that i) OATPs can be a potential molecular target for hormone dependent breast cancers in post menopausal patients and ii) E3S can be used a ligand for actively targeting hormone dependent breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 377. doi:1538-7445.AM2012-377
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".