Background: PGRMC1 (progesterone receptor membrane component 1) is a highly conserved heme binding protein, which is overexpressed especially in hormone receptor-positive breast cancer and plays an important role in breast carcinogenesis. Nevertheless, little is known about the mechanisms by which PGRMC1 drives tumor progression. The aim of our study was to investigate the involvement of PGRMC1 in cholesterol metabolism to detect new mechanisms by which PGRMC1 can increase lipid metabolism and alter cancer-related signaling pathways leading to breast cancer progression. Methods: The effect of PGRMC1 overexpression and silencing on cellular proliferation was examined in vitro and in a xenograft mouse model. Next, we investigated the interaction of PGRMC1 with enzymes involved in the cholesterol synthesis pathway such as CYP51, FDFT1, and SCD1. Further, the impact of PGRMC1 expression on lipid levels and expression of enzymes involved in lipid homeostasis was examined. Additionally, we assessed the role of PGRMC1 in key cancer-related signaling pathways including EGFR/HER2 and ERα signaling. Results: Overexpression of PGRMC1 resulted in significantly enhanced proliferation. PGRMC1 interacted with key enzymes of the cholesterol synthesis pathway, alters the expression of proteins, and results in increased lipid levels. PGRMC1 also influenced lipid raft formation leading to altered expression of growth receptors in membranes of breast cancer cells. Analysis of activation of proteins revealed facilitated ERα and EGFR activation and downstream signaling dependent on PGRMC1 overexpression in hormone receptor-positive breast cancer cells. Depletion of cholesterol and fatty acids induced by statins reversed this growth benefit. Conclusion: PGRMC1 may mediate proliferation and progression of breast cancer cells potentially by altering lipid metabolism and by activating key oncogenic signaling pathways, such as ERα expression and activation, as well as EGFR signaling. Our present study underlines the potential of PGRMC1 as a target for anti-cancer therapy.

The dependence of the photocarrier radiometric (PCR) signal on the intensity of exciting superbandgap laser radiation was investigated. It was shown that the amplitude of the PCR signal exhibits a supralinear dependence on laser intensity <mml:math display="inline"><mml:mrow><mml:msubsup><mml:mi>I</mml:mi><mml:mrow><mml:mn>0</mml:mn></mml:mrow><mml:mi>β</mml:mi></mml:msubsup></mml:mrow></mml:math>I0β , with nonlinearity coefficient/exponent β such that <mml:math display="inline"><mml:mrow><mml:mn>1</mml:mn><mml:mo>≤</mml:mo><mml:mi>β</mml:mi><mml:mo>≤</mml:mo><mml:mn>2</mml:mn></mml:mrow></mml:math>1≤β≤2 . The power dependence of the amplitude is an important indicator of the photoexcited carrier recombination physics in semiconductors ranging between monopolar <mml:math display="inline"><mml:mrow><mml:mo>(</mml:mo><mml:mi>β</mml:mi><mml:mo>=</mml:mo><mml:mn>1</mml:mn><mml:mo>)</mml:mo></mml:mrow></mml:math>(β=1) and bipolar <mml:math display="inline"><mml:mrow><mml:mo>(</mml:mo><mml:mi>β</mml:mi><mml:mo>=</mml:mo><mml:mn>2</mml:mn><mml:mo>)</mml:mo></mml:mrow></mml:math>(β=2) limits. The study was made with laser beams of varying wavelength, power, and spotsize and with semiconductor silicon wafers with different transport parameters, especially recombination lifetime. One-dimensional and three-dimensional models of the nonlinear PCR signal dependence on β vs modulation frequency were developed. It was found that the conventional linear approach using <mml:math display="inline"><mml:mrow><mml:mi>β</mml:mi><mml:mo>=</mml:mo><mml:mn>1</mml:mn></mml:mrow></mml:math>β=1 is not always consistent with experimental slopes of amplitude vs power and it may yield erroneous values of the electronic transport properties. Consideration of the fundamental and second harmonic amplitudes and phases of the PCR signal showed that the physical origin of the nonlinear dependence of the PCR amplitude on laser intensity is consistent with high-optical-injection of free-carriers in the semiconductor. The value of β can also be determined by the second harmonic-to-fundamental-amplitude ratio and is controlled by the carrier relaxation time dependence on the optically injected excess diffusive photocarrier density wave.

Time-domain and lock-in rate-window photocarrier radiometry (PCR) configurations are introduced both experimentally and theoretically to investigate the responses of $p$ - and $n$ -type Si wafers under a repetition-period-scanned square-wave-modulated super-band-gap laser beam which produces free excess photocarriers. The complete asymmetric time-domain carrier diffusion and recombination boundary-value problem with different front- and back-surface recombination velocities was solved in terms of the full spectrum of spatial eigenmodes and used to fit the time-domain data. The accurate measurement of the photocarrier transport properties (bulk lifetime, surface recombination velocities, and ambipolar diffusivity) was found to require the linear superposition of all the effective decay lifetimes associated with the eigenmode spectrum. The effects of the infinite prior pulse train to the current photocarrier radiometric response wave form were quantified and were found to be very important for certain ranges of transport parameters, pulse durations, and repetition periods. The time-domain formalism was further used to develop a theory for lock-in rate-window photocarrier radiometry. The application of the theory to the experimental results shows that they retain the time-domain character of the photocarrier generation and recombination processes, with data quality and signal-to-noise ratio superior to coaddition-averaged transients, especially in the case of samples exhibiting very low time-domain PCR signals.