The direct claim of the paper is that the activity of pyrrolidon carboxypeptidase (Pcp) is differently affected by treatments with compounds such as estradiol or tamoxifen in estrogen-dependent versus estrogen-independent breast cancer cells. Specifically, estradiol decreases the activity of Pcp in MCF-7 cells but does not affect its activity in EVSA-T cells, whereas tamoxifen decreases the activity of Pcp in EVSA-T cells but does not affect its activity in MCF-7 cells. The paper references previous studies that support the broader claim that Pcp might play an important role in breast cancer pathogenesis. If this broader claim is verified as true, Pcp could be utilized as a biomarker for breast cancer pathology as well as a target for drug activity. In this case, information such as that presented in this paper will be essential to utilizing Pcp for these purposes.

There are no papers that weaken the claims to the originality of this one to my knowledge.

Claims are properly placed in the context of previous literature. The Introduction is very light, but the primary exposition of context is given in the Discussion.

The results support the direct claim, namely, that the activity of pyrrolidon carboxypeptidase is differently affected by treatments with estradiol or tamoxifen in estrogen-dependent versus estrogen-independent breast cancer cells. The results do not address the claim advanced in other papers that pyrrolidon carboxypeptidase plays an important role in breast cancer pathogenesis.

No protocol is provided; only cell studies were conducted.

The methodology is valid. Sufficient detail is provided for reproduction of experiments. There is no mention in methodology of number of trials performed. Experiments should be repeated on separate days at least in triplicate to verify reproducibility of results. If experiments were performed in triplicate, this should be mentioned in the Methods section.

The primary need to strengthen this paper is to demonstrate that pyrrolidon carboxypeptidase does in fact play an important role in breast cancer pathogenesis. The significance of the results in this paper hinges on this postulate. I cannot suggest a method to investigate this postulate without conducting further review of literature on the subject. However, it seems a subject worth further investigation.

This paper does not seem outstanding in its discipline. It is a good study investigating a specific question, but its results only minimally contribute to the discovery and definition of a potential new method of breast cancer diagnosis and therapy.

I enjoyed reading this paper. My key recommendation regarding this paper, elaborated previously, is to replicate all studies to verify reproducibility of results. Below are additional recommendations regarding presentation of the paper:

(1) The Results section appears to be missing content that was intended to be there. Consequently, the Results section is unclear and confusing to read.

(2) There are multiple (>10) formatting, spelling, and grammar errors in the paper. The paper would be more accessible to readers if these errors were corrected. I would be happy to list the errors I noticed if this is requested.

I have conducted cancer therapy research with NSF funding. In addition, I have taken graduate courses in drug delivery and pharmaceutics.

This paper highlights the potential of pyrrolidon carboxypeptidase activity as a potential drug target against hormone sensitive breast cancer. The work shown here clearly highlights the relationship of Pcp and its metabolic products on hormone sensitive as well as non-hormone sensitive breast cancer. It would be interesting to observe the detailed mechanisms involved in the activity of this interaction on other key targets on Eastrogen Receptor signalling such as AR, C3 (Complement component 3), CCND1, CTSD (cathepsin D), ESR1, ESR2, GATA3, HSPB1 (HSP28), KRT18, KRT19 (Keratin 19), PGR, SERPINA3 (a1-antichmotrypsin), SLC7A5, STC2, TFF1 (pS2). This will definitely increase the value of this work.

Yes