K-Ras 4A Transcript variant is up-regulated in eutopic endometrium of endometriosis patients during proliferative phase of menstrual cycle

article OA: closed CC0 ⤵ 5 in-corpus citations
AI-generated summary by claude@2026-07, 2026-07-14

K-Ras 4A transcript expression was 2.7-fold higher in the eutopic endometrium of endometriosis patients compared to controls, particularly during the proliferative phase.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

AI-generated deep summary by claude@2026-07, 2026-07-14 · read from full text

This study investigated expression of the K-Ras isoforms K-Ras 4A and K-Ras 4B in eutopic endometrium from women with endometriosis and non-endometriosis controls, using RT-PCR and quantitative real-time PCR with GAPDH normalization. The authors found that both K-Ras 4A and K-Ras 4B transcripts were present, and that K-Ras 4A mRNA expression was 2.7-fold higher in endometriosis samples, with the overexpression occurring mainly during the proliferative phase of the menstrual cycle. A key limitation acknowledged by the study is that the work is based on transcript levels rather than functional assays, leaving mechanisms inferred rather than directly demonstrated. This paper is centrally about endometriosis — it focuses on up-regulated K-Ras 4A transcript variants in eutopic endometrium of endometriosis patients, particularly in the proliferative phase.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

AimsK-Ras transcripts comprise two main isoforms: K-Ras 4A and K-Ras 4B, which act differently. The expression of both isoforms was reported in many human tissues. However, K-Ras 4B was the major expressed transcript variant. An increased expression of K-Ras 4B mRNA was reported in eutopic endometrium of endometriosis patients. In this way, we aimed to study the expression of K-Ras 4A transcript in eutopic endometrium related to endometriosis.MethodsEmploying exon4-flanking primers, K-Ras isoforms were simultaneously amplified in a RT-PCR reaction. Quantitative real-time PCR was performed using GAPDH as an internal control. K-Ras 4A transcript expression in eutopic endometrium was analyzed by ΔΔC T method.ResultsWe identified existence of both of K-Ras 4A and K-Ras 4B in eutopic endometrium of patients and controls. Quantitative real-time analysis demonstrated that K-Ras 4A expression was 2.7-fold higher in endometriosis than non-endometriosis eutopic samples. Interestingly, this overexpression mainly occurs through the proliferative phase of menstrual cycle.ConclusionThe findings bring to light the eminent role of K-Ras 4A in endometriosis. This splice variant which is known for promoting apoptosis could be an effective factor in balance between proliferation and death of eutopic endometrial cells.
Full text 6,835 characters · extracted from oa-doi-fallback · 5 sections · click to expand

Abstract

Aims K-Ras transcripts comprise two main isoforms: K-Ras 4A and K-Ras 4B, which act differently. The expression of both isoforms was reported in many human tissues. However, K-Ras 4B was the major expressed transcript variant. An increased expression of K-Ras 4B mRNA was reported in eutopic endometrium of endometriosis patients. In this way, we aimed to study the expression of K-Ras 4A transcript in eutopic endometrium related to endometriosis.

Methods

Employing exon4-flanking primers, K-Ras isoforms were simultaneously amplified in a RT-PCR reaction. Quantitative real-time PCR was performed using GAPDH as an internal control. K-Ras 4A transcript expression in eutopic endometrium was analyzed by ΔΔC T method.

Results

We identified existence of both of K-Ras 4A and K-Ras 4B in eutopic endometrium of patients and controls. Quantitative real-time analysis demonstrated that K-Ras 4A expression was 2.7-fold higher in endometriosis than non-endometriosis eutopic samples. Interestingly, this overexpression mainly occurs through the proliferative phase of menstrual cycle.

Conclusion

The findings bring to light the eminent role of K-Ras 4A in endometriosis. This splice variant which is known for promoting apoptosis could be an effective factor in balance between proliferation and death of eutopic endometrial cells. Similar content being viewed by others

References

Rogers PA, D’Hooghe TM, Fazleabas A, Giudice LC, Montgomery GW, Petraglia F, Taylor RN (2013) Defining future directions for endometriosis research: workshop report from the 2011 World Congress of Endometriosis in Montpellier. France Reprod Sci 20(5):483–499 Haas D, Chvatal R, Reichert B, Renner S, Shebl O, Binder H, Wurm P, Oppelt P (2012) Endometriosis: a premenopausal disease? Age pattern in 42,079 patients with endometriosis. Arch Gynecol Obstet 286(3):667–670 Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, Lessey BA, Giudice LC (2007) Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology 148(8):3814–3826 Dinulescu DM, Ince TA, Quade BJ, Shafer SA, Crowley D, Jacks T (2005) Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 11(1):63–70 Vercellini P, Trecca D, Oldani S, Fracchiolla NS, Neri A, Crosignani PG (1994) Analysis of p53 and ras gene mutations in endometriosis. Gynecol Obstet Invest 38(1):70–71 Otsuka J, Okuda T, Sekizawa A, Amemiya S, Saito H, Okai T, Kushima M, Tachikawa T (2004) K-ras mutation may promote carcinogenesis of endometriosis leading to ovarian clear cell carcinoma. Med Electron Microsc 37(3):188–192 Kalnina Z, Zayakin P, Silina K, Line A (2005) Alterations of pre-mRNA splicing in cancer. Genes Chromosomes Cancer 42(4):342–357 Plowman SJ, Berry RL, Bader SA, Luo F, Arends MJ, Harrison DJ, Hooper ML, Patek CE (2006) K-ras 4A and 4B are co-expressed widely in human tissues, and their ratio is altered in sporadic colorectal cancer. J Exp Clin Cancer Res 25(2):259–267 Hancock JF (2003) Ras proteins: different signals from different locations. Nat Rev Mol Cell Biol 4(5):373–384 Plowman SJ, Williamson DJ, O’Sullivan MJ, Doig J, Ritchie AM, Harrison DJ, Melton DW, Arends MJ, Hooper ML, Patek CE (2003) While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable. Mol Cell Biol 23(24):9245–9250 Voice JK, Klemke RL, Le A, Jackson JH (1999) Four human ras homologs differ in their abilities to activate Raf-1, induce transformation, and stimulate cell motility. J Biol Chem 274(24):17164–17170 Grechukhina O, Petracco R, Popkhadze S, Massasa E, Paranjape T, Chan E, Flores I, Weidhaas JB, Taylor HS (2012) A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis. EMBO Mol Med 4(3):206–217 Laudanski P, Szamatowicz J, Kowalczuk O, Kuzmicki M, Grabowicz M, Chyczewski L (2009) Expression of selected tumor suppressor and oncogenes in endometrium of women with endometriosis. Hum Reprod 24(8):1880–1890 Farahani MS, Shahbazi S, Moghaddam SA, Mahdian R(2014) Evaluation of KRAS gene expression and LCS6 variant in genomic and cell-free DNA of Iranian women with endometriosis. Reprod Sci Wang Y, You M (2001) Alternative splicing of the K-ras gene in mouse tissues and cell lines. Exp Lung Res 27(3):255–267 Koera K, Nakamura K, Nakao K, Miyoshi J, Toyoshima K, Hatta T, Otani H, Aiba A, Katsuki M (1997) K-ras is essential for the development of the mouse embryo. Oncogene 15(10):1151–1159 Johnson L, Greenbaum D, Cichowski K, Mercer K, Murphy E, Schmitt E, Bronson RT, Umanoff H, Edelmann W, Kucherlapati R et al (1997) K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Dev 11(19):2468–2481 Hurst BS, Shimp KE, Elliot M, Marshburn PB, Parsons J, Bahrani-Mostafavi Z (2014) Molecular evaluation of proliferative-phase endometrium may provide insight about the underlying causes of infertility in women with endometriosis. Arch Gynecol Obstet 289(5):1119–1124 Critchley HO, Saunders PT (2009) Hormone receptor dynamics in a receptive human endometrium. Reprod Sci 16(2):191–199 Bromer JG, Aldad TS, Taylor HS (2009) Defining the proliferative phase endometrial defect. Fertil Steril 91(3):698–704 Plowman SJ, Arends MJ, Brownstein DG, Luo F, Devenney PS, Rose L, Ritchie AM, Berry RL, Harrison DJ, Hooper ML et al (2006) The K-Ras 4A isoform promotes apoptosis but does not affect either lifespan or spontaneous tumor incidence in aging mice. Exp Cell Res 312(1):16–26 Vaskivuo TE, Stenback F, Karhumaa P, Risteli J, Dunkel L, Tapanainen JS (2000) Apoptosis and apoptosis-related proteins in human endometrium. Mol Cell Endocrinol 165(1–2):75–83 Kokawa K, Shikone T, Nakano R (1996) Apoptosis in the human uterine endometrium during the menstrual cycle. J Clin Endocrinol Metab 81(11):4144–4147 Dmowski WP, Ding J, Shen J, Rana N, Fernandez BB, Braun DP (2001) Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis. Hum Reprod 16(9):1802–1808 Acknowledgments The authors acknowledge the contribution of the subjects in this study. This work was supported by Research Deputy of Tarbiat Modares University Conflict of interest The authors declare that they have no conflict of interest. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Shahrabi-Farahani, M., Shahbazi, S., Mahdian, R. et al. K-Ras 4A Transcript variant is up-regulated in eutopic endometrium of endometriosis patients during proliferative phase of menstrual cycle. Arch Gynecol Obstet 292, 225–229 (2015). https://doi.org/10.1007/s00404-014-3596-7 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-014-3596-7

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Menstrual Cycle Proto-Oncogene Proteins ras Proteins Adult Case-Control Studies DNA Primers DNA Primers Endometriosis Endometriosis Endometrium Female Humans Menstrual Cycle Middle Aged Proto-Oncogene Proteins Proto-Oncogene Proteins p21(ras) ras Proteins Real-Time Polymerase Chain Reaction

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (24)

Cited by (5)

Source provenance

europepmc
last seen: 2026-07-27T06:15:28.040536+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:18:04.362919+00:00
unpaywall
last seen: 2026-06-13T06:42:57.164913+00:00
License: CC0 · commercial use OK